final transfusion talk wac 11_2007
TRANSCRIPT
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All Bleeding Eventually Stops:
Are Outcomes Changed by
Transfusion?
Colleen Gorman Koch, MD, MS, FACC
Cardiothoracic Anesthesia and
Outcomes Research
Cleveland Clinic
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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.
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• 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 withinfectious transmission and
association between
morbidity and RBC became focus
of research
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Limited Resource:
Challenges us to think more conservatively
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Risks
Morbidity and MortalityOutcomes
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Morbidity and Mortality:
Cohort Investigations
Transfusion
Infection:
Sternal wound
Pneumonia
Pulmonary
dysfunction
Renal
insufficiencyMSOF
Mortality:Short
Long-term
• N, Outcome, RBC binary, heterogeneity, statistics, generalize
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Koch, et al., Critical Care Medicine 2006;34:1608-1616
Morbidity and Mortality
in (N=11,963) Isolated CABG
•Increased risk for every morbid outcome•Dose-dependent relationship between each unit and events
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Frequency Histogram for RBC Units
Transfused
Koch et al., Critical Care Medicine 2006;34:1608-1616
•48% transfused
•Most commonly
1-2 units transfused
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Patient and Procedural Variables
Related to RBC TransfusionKoch et al., Critical Care Medicine 2006;34:1608-1616
•Older, smaller,
lower pre-op HCT,comorbidity,
clinical presentation:
emergency, NYHA,
preop IABP; reoperationlonger clamp times
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Infection:End-points: bacteremia, septicemia,
superficial and deep sternal wound infections
Banbury, et al., JACC 2006;202:131
• N=15,592
Independent risk for postoperative infection
•(55%)transfused
•Dose-dependent
relationship
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N=1915
N=649
transfused
N=546
Propensitymatched
Engoren, et al. Annals of Thoracic Surgery 2002
Risk factor for 5 year mortality after CTS
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N=10,289
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 parametricdecomposition method accounts
for non-proportionality;
simultaneously models time-
varying hazard and risk factors
Transfusion and Long-term
Survival
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Koch et al., Annals of Thorac Surg 2006;82:13-20
Quality of life: DASI (N=7,321)
•Reductions in
functional recovery
paralleled RBC
transfused
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Annals of Thorac Surg 2006;82:13-20
N=7,321
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Other Issues…
• Leukocyte-reduced status
• Age of red cells
• Blood substitutes
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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
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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.
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Dose-response Relationship Between Max Days
Storage and Probability of Composite Outcome
Increasing linear trend, particularly for those receiving units > 14 days storage duration
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Storage Duration and Outcome
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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
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Predicted Survival and Maximal Age with
Hazard Decomposition Model
1 day = orange; 15 days = red; 30 days = blue; and 42 days = black
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PNAS 2007;104
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Tissue Oxygenation
• Local microcirculatory control mechanisms areimportant in the restoration of tissue oxygenation.
• Regulatory mechanisms for maintaining adequatetissue oxygen concentration are not wellunderstood.
• Role of oxygen sensor in tissue? Red cell?
• Red cell may play a role as oxygen carrier andoxygen sensor, during hypoxia it may modulateflow by release of vasodilatory nitric oxide.
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Tissue Oxygenation
• New findings indicate that red cell function is
more complex than previously assumed.
• Advantage of oxygen sensing by red cells is thatallows 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.
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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
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New Donation Strategy?
Give Blood, Play Hockey
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