Transcript Blood Transfusion – Controversies of Red Cell Transfusion

Blood Transfusion:
New Guidelines
Joint Surgery and Anesthesiology Grand Rounds
July 2, 2009
Paul Picton MD
Lena M. Napolitano MD
Andrew Rosenberg MD
Perioperative Transfusion
Triggers
Paul Picton MD MRCP FRCA
Assistant Professor
Director, Transplant Anesthesia
Changes in cardiac output (A) oxygen extraction (B) oxygen delivery (C) and
oxygen consumption (D) as hemoglobin decreases in humans and animals
Klein HG, et al. Lancet 2007; 370:415-426
Anemia in Healthy Awake
Volunteers
• Critical hemoglobin threshold unknown in
humans
• At 5 g/dL - VO2 maintained but ST
changes (5%) and memory formation
impaired
• At 6 g/dL - decline in cognitive function
Lieberman, et al. Anesthesiology 2000
Do Nothing Study
• Retrospective study of 300 JW who underwent surgery
from 1981 - 1994
• Even after adjusting for age, cardiovascular disease and
APACHE score, odds of death increased by 2.5 times for
each gram of Hb below 8 g/dL
Transfusion. 2002 Jul;42(7):812-8
Do Nothing Study
• Retrospective study of 300 JW who underwent surgery
from 1981 - 1994
• Even after adjusting for age, cardiovascular disease and
APACHE score, odds of death increased by 2.5 times for
each gram of Hb below 8 g/dL
Transfusion. 2002 Jul;42(7):812-8
The TRICC Study
• Enrolled 838 euvolemic, anemic, critically ill pts
who were admitted to 1 of 25 Canadian ICUs
• Patients were stratified according to center and
disease severity (APACHE II) and placed into
one of two groups
– Restrictive group: Transfuse if Hb < 7 and maintain
between 7 and 9
– Liberal group: Transfuse if Hb < 10 and maintain
between 10 and 12
• The primary outcome measure was death from
all causes in the 30 days after randomization
Herbert PC, et al. NEJM 1999
TRICC - Design
The TRICC Study
No difference 30 day mortality
In “healthy” (APACHE II < 20) and young
(<55yrs) patients
Transfusion increased mortality
Herbert PC, et al. NEJM 1999
The TRICC Study
8.7% vs 16.1%
5.7% vs 13.0%
Herbert PC, et al. NEJM 1999
The TRICC Study
• Average red cell units per patient:
2.6 ± 4.1 vs. 5.6 ± 5.3 (p < 0.01)
• Average daily Hb concentrations:
8.5 ± 0.7 g/dl vs. 10.7 ± 0.7 g/dl (p < 0.01)
TRICC Sub Group Analyses
Trauma (n = 203)
McIntyre LA, et al. J Trauma 2004;57:563-568
Moderate to severe head injury (n = 67)
McIntyre LA, et al. Neurocrit Care 2006;05:4-9
Cardiovascular disease (n = 357)
Herbert PC, et al. Crit Care Med 2001; 29(2):227-234
Mechanical ventilation (n = 713)
Hebert PC, et al. Chest 2001 June;119(6):1851.
No difference in outcomes
“A restrictive red blood cell transfusion
strategy generally appears to be safe in
most critically ill patients with cardiovascular
disease…
with the possible exception of
patients with acute myocardial infarction and
unstable angina.”
CRIT Study
• Prospective, multiple center, observational
cohort study of 4,892 ICU pts in the US
• Propensity score matched
• Designed to examine the relationship of anemia
and RBC transfusion with clinical outcomes
• Almost 95% of patients admitted to the ICU have
a Hb level below “normal” by day 3
• In total, 11,391 RBC units were transfused.
• Overall, 44% of pts admitted to the ICU received
one or more RBC units while in the ICU
Crit Care Med. 2004 Jan;32(1):39-52
CRIT Results
35% of Blood transfused in
patients with Hgb  9
The mean pre-transfusion Hb
was 8.6 ± 1.7 g/dL
RBC transfusion was independently
associated with higher mortality (OR
1.65 CI 1.35-2.03). OR 2.62 if 3-4 units
transfused p < 0.0001
Hematocrit versus Postop Morbidity & Ischemia
ST
Sx
Percent of Patients
100
80
60
40
20
0
23-25
n = 27 high-risk pts
undergoing infra-inguinal
arterial bypass
26-28
29-31
32-34
35-37
Hematocrit (%)
Nelson A, Fleischer L, et al. Crit Care Med 1993
•
•
•
•
•
2001
Retrospective cohort
Cooperative Cardiovascular Project
78,974 patients ≥ 65 yrs acute MI
30 day mortality
Blood transfusion associated with ↓ mortality if Hct < 30%
• Analysis of 24,112 enrollees in 3 large
international trials of patients with acute
coronary syndromes
• Association between transfusion and
outcome
• Cox proportional hazards modeling
• Main outcome = 30 day mortality
Rao SV et al. JAMA. 2004;292:1555-1562
Blood Transfusion and Clinical
Outcome in Acute Coronary Syndrome
Transfusion
Adjusted
hazard ratio
3.94
(3.26-4.75)
No Transfusion
Rao SV et al. JAMA. 2004;292:1555-1562
• Meta-analysis of observational studies
• 45 studies - 272,596 patients
• Multivariate analysis correcting for age and
illness severity
• Outcome measures:
–
–
–
–
Mortality
Infection
Multi-organ dysfunction
ARDS
Crit Care Med 2008;36(9):2667-74
Results
Association between blood
transfusion and the risk of
death (OR & 95% CI). Pooled
OR 1.7 (95% CI 1.4-1.9)
Crit Care Med 2008;36(9):2667-74
Association between blood
transfusion and the risk of
infectious complications (OR
& 95% CI). Pooled OR 1.8
(95% CI 1.5-2.2)
Results
Association
between blood
transfusion and
the risk of ARDS
(OR & 95% CI).
Pooled OR 2.5
(95% CI 1.6-3.3)
Crit Care Med 2008;36(9):2667-74
Financial Burden
$20
$14.97
$15
$12.56
Millions
$11.08
$12.56
$10.76
UMHHC direct cost of blood
products
$10
$5
$0
FY'04
FY'05
FY'06
FY'07
FY'08
Based on data from UMHHC cost accounting system.
Cost includes cost of blood products and allocated
costs of labor
Cost per case
% of cases using blood
$1,000
100
$800
$696
$602
$600
$553
80
$590
$534
60
44%
$400
40
$200
20
$0
0
FY'04 FY'05 FY'06 FY'07 FY'08
43%
44%
46%
47%
FY'04 FY'05 FY'06 FY'07 FY'08
Summary
• Post op Hct 15 - very high mortality
• At Hct 18 - cognitive dysfunction in healthy
volunteers
• Utilization of a transfusion trigger 21 (mean Hct
25) - confers survival benefit for those < 55 yrs
and those with an APACHE < 20
• A liberal transfusion policy - trigger 30 (mean
Hct 32) does not benefit patients on critical care
• At Hct 27 - ST changes in high risk patients.
Summary
• Transfusion may benefit patients during
acute coronary syndromes if Hct < 25-29
• There is only rarely an indication to
transfuse ANY patient with a Hct ≥ 30
• Blood transfusions are not risk free
• Decreasing transfusion may not only
decrease cost but also improve outcome
Closing Comments
• Good prospective data limited to critical
care setting
• Considerable scope for differences in
opinion
• Concerning intra-operative transfusion best to come to some agreement pre op
and remain in communication
• Give RBC’s as single units when possible
• Treat the patient not the Hct
Univ. Michigan Adult Blood
Transfusion Guidelines: 2009
Lena M. Napolitano MD, FACS, FCCP, FCCM
Professor of Surgery
Division Chief, Acute Care Surgery
Department of Surgery
University of Michigan
Ann Arbor, MI
Adult Blood Transfusion
Clinical Guidelines
Plan and Guideline endorsed by ECCA on March 24, 2009
Project Overview & Scope Of Work
Blood Utilization lean project work was commissioned by both OCA &
Hospital Administration, under the oversight of Dr. Skip Campbell
Team Make-Up
Dr. Tim Laing, Internal Medicine/OCA
Dr. Rob Davenport, Blood Bank
Lena Napolitano, MD-Surgeon/ICU
Bill Palazzolo, Dir. Pre-Op Clinic
Paul Picton, MD-Anest/Transplant
Shon Dwyer, AHD
Andrew Rosenburg, MD-Anest/Carelink
Vinita Bahl, SMT
Jeff Rohde, MD-Int. Medicine
Brendon Weil, Lean Coach
Ryen Fons, House Officer-Anest.
Gail Sinwell, Lean Coach
Russel Butler, Perfusion, CVC
Barb Chapman, CIDSS
Project Goal: To develop standard policies & practices leading to: improved
patient outcomes through the appropriate use of blood products and gain
process efficiencies by removing waste and delays in the blood dispensing &
administration process
Guidelines for Blood
Transfusion: PRBCs

These guidelines are intended to ensure that the most
appropriate, efficient and safe use of the blood supply is
achieved

To establish evidence-based criteria for the transfusion of
blood components

Every indication for the use of blood products cannot be
anticipated

These guidelines are not intended to override physician
judgement
Guidelines for Blood
Transfusion: PRBCs

Hemodynamically stable anemia without acute coronary syndrome:
hemoglobin trigger less than 7 g/dL, with a transfusion goal to
maintain hemoglobin 7 – 9 g/dL.

Acute hemorrhage with evidence of hemodynamic instability or
inadequate oxygen delivery

Symptomatic (tachycardia, tachypnea, postural hypotension) anemia (Hb <
10 g/dL) not explained by other causes

Chronic Tx-dependent bone marrow syndromes: Hb < 10 g/dL.

Transfusion or exchange transfusion for severe sickle syndromes.

Hemodynamically stable anemia with ischemic heart disease: current
evidence does not support routine transfusion in non-ST segment elevation
acute coronary syndromes; although in ST-segment elevation myocardial
infarction Tx may be beneficial.
Guidelines for Blood
Transfusion: PRBCs

RBCs should be administered as single units for most operative
and inpatient indications (transfuse and reassess strategy) except
for ongoing blood loss with hemodynamic instability.

Tx decisions are clinical judgments that should be based on the
overall clinical assessment of the individual patient. Transfusion
decisions should not be based on laboratory parameters alone.

Routine premedication is not advised unless the patient has a
history of previous transfusion reactions. Premedication has not
been shown to reduce the risk of transfusion reactions.
EAST / SCCM Blood Tx Guidelines
CLINICAL PRACTICE GUIDELINE:
RED BLOOD CELL TRANSFUSION IN ADULT TRAUMA and CRITICAL CARE
Lena M. Napolitano MD
Stanley Kurek DO
Fred A. Luchette MD
For the EAST Practice Management Workgroup and
The American College of Critical Care Medicine Taskforce of the SCCM
The EAST Practice Management Workgroup
Gary L. Anderson DO
Michael R. Bard MD
William Bromberg MD
William C. Chiu MD
Mark D. Cipolle MD, PhD
Keith D. Clancy MD
Lawrence Diebel MD
William S. Hoff MD
K. Michael Hughes DO
Imtiaz Munshi MD
Donna Nayduch RN, MSN, ACNP
Rovinder Sandhu MD
Jay A. Yelon MD
In press.
November 2009
Crit Care Med
The American College of Critical Care Medicine Taskforce of the SCCM
Howard L. Corwin MD
Philip S. Barie MD
Samuel A. Tisherman MD
Paul C. Hebert MD, MHSc
Risks of Blood Transfusion

Viral transmission

Acute transfusion reactions

Immunosuppression

Acute inflammatory response
Noninfectious Hazards
Immunosuppression
Infection
Risk of Infection per
Unit Transfused
Decline in HIV, HBV, HCV Risks
of Transmission via Blood Tx
1:100
HIV
HCV
HBV
1:1000
1:10,000
1:100,000
1:1,000,000
1:10,000,000
1983 1985
Revised Donor
Deferral Criteria
1987
1989
Non-A, Non-B
Hepatitis
Surrogate Testing
HIV Antibody
Screening
Busch MP, et al. JAMA. 2003;289:959-62.
1991 1993
Year
HCV Antibody
Screening
1995
1997
p24 Antigen
Testing
1999 2001
HCV and HIV
Nucleic Acid
Testing
Risks of Transfusion:
Infectious Disease

HIV = 1 in 1.8 million

HCV = 1 in 1.6 million

HBV = 1 in 220,000
HIV = human immunodeficiency virus.
HCV = hepatitis C virus.
HBV = hepatitis B virus.
Busch MP, et al. JAMA. 2003;289:959-62.
Serious Hazards of Transfusion
Post-transfusion
purpura
Acute lung injury
Graft vs host
disease
6%
8%
2%
Delayed
transfusion
reaction
3%
Transfusion-transmitted
infections
14%
53%
Incorrect blood/
component
transfused
15%
Acute
transfusion
reaction
Williamson LM, et al. BMJ. 1999;319:16-9.
Based on 366 spontaneously-reported
deaths/major complications between
October 1996 and September 1998
in the UK and Ireland.
Risks of Blood Transfusion
Minor allergic reactions
1:100
Bacterial infection (platelets)
1:2,500
Viral hepatitis
1:5,000
Hemolytic transfusion reaction
1:6,000
HTLV I/II infection
1:200,000
Acute lung injury
TRALI 1:5,000
1:500,000
Anaphylactic shock
1:500,000
Fatal hemolytic reaction
1:600,000
Graft-vs-host disease
Rare
Immunosuppression
Unknown
HTLV = human T-cell leukemia-lymphoma virus.
Klein HG. Am J Surg. 1995. 170;6A(suppl):21S-26S.
Immune Effects of Blood
•
Immunologic effects of autologous and
allogenic blood transfusions:
- Decreased T-cell proliferation
- Decreased CD3, CD4, CD8 T-cells
- Increased Soluble cytokine receptor
- sTNF-R, sIL-2R
Increased Serum neopterin
Increased Cell-mediated lympholysis
Increased TNF-alpha
- Increased suppressor T-cell activity
- Reduced natural killer cell activity
-
TRIM – Transfusion-associated Immunomodulation
McAlister FA, et al, British Journal of Surgery 1998; 85: 171-178
Innerhofer et al. Transfusion 1999 Oct;39(10):1089
Blood Tx Increases Risk of
Postoperative Bacterial Infection



20 peer-reviewed studies, 1986-2000
N = 13,152 (Tx 5215, No-Tx 7937)
Association of Blood Tx to Infection
– Common OR 3.45 (range 1.43-15.15)
– 17 of 20 studies with p < 0.05

Trauma subgroup
– Common OR 5.26 (range 5.03-5.43)
– All studies with p < 0.05 (0.005 – 0.0001)
– Blood Tx associated with greater risk in trauma pts
Hill GE, Minei JP et al. J Trauma 2003;54:908-914

Prospective cohort
study, n=2085

Project Impact

Nosocomial Infections:
14.3% vs. 5.8%, p <
0.001
Taylor RW et al.
Crit Care Med 2006;
34:2302–2308
15,592 Cardiovascular operations
 Infection endpoints bacteremia, SSI
 55% of pts received PRBCs, 21% plts, 13%
FFP, 3% cryoprecipitate
 Increased RBC tx associated with increased
infection (p < 0.0001), confirmed by
logistic regression analysis.

J Am Coll Surg 2006;202:131-138
Leukoreduction does not diminish tx-associated Microchimerism
Reed W, et al. Semin Hematol 2007:44:24-31
Utter G et al. Transfusion 2006 Nov;46(11):1863-9
Gould S et al. Am J Crit Care; Jan 2007;16(1):39-48
Why is blood transfusion
NOT associated with
improved outcome?
Stored RBCs

Decreased RBC deformability

Decreased 2,3, DPG

Metabolic acidosis

Altered oxygen carrying capacity

Increased red cell death with
increased age of blood (~30%
dead)

No improvement in oxygen
utilization at the tissue level
Age of Blood
Poor Efficacy of Blood Tx

RBCs stored > 15 days lose deformability and ATP

Altered capillary lumen size (decreased cross-sectional
diameter) in critically ill patients

Increased “stickiness” (adherence) of RBCs to altered
endothelium in the microcirculation of critically ill pts.
Schechter, Gladwin, NEJM April 10, 2003
Distribution of Transfused Units
by Age of Blood – CRIT Study
60% of Blood transfused
is > 20 days old
Percentage of Patients
35%
30%
25%
20%
15%
10%
5%
0%
0 - 10
10 - 20
20 - 30
30 - 40
Oldest Age of Blood in Days
In Trauma Subset, 68% of blood is > 20 days old
> 40
March 20, 2008





The median duration of storage
was 11 days for newer blood and
20 days for older blood.
Patients who were given older
units had higher rates of inhospital mortality (2.8% vs.
1.7%, P = 0.004), intubation
beyond 72 hours (9.7% vs. 5.6%,
P<0.001), renal failure (2.7% vs.
1.6%, P = 0.003), and sepsis or
septicemia (4.0% vs. 2.8%, P =
0.01).
A composite of complications
was more common in patients
given older blood (25.9% vs.
22.4%, P = 0.001).
Similarly, older blood was
associated with an increase in
the risk-adjusted rate of the
composite outcome (P = 0.03).
At 1 year, mortality was
significantly less in patients
given newer blood (7.4% vs.
11.0%, P<0.001).
Composite Outcome:
In-hospital mortality
And Complications
(STS)
Age of Blood Evaluation (ABLE)
ABLE Study-Hypothesis
The use of fresh red cells as compared to
standard issue red cells will lead to
significant improvement in morbidity and
mortality
Age of Blood Evaluation (ABLE) in the
resuscitation of critically ill patients
International Study, CIHR, NIH, others
Projected n = 6800
ABLE……Something about the design?
Study Design: Randomized double-blind
controlled clinical trial.
Setting: 30 Canadian tertiary care
intensive care and trauma units. Additional
study sites in the US, UK, Europe and
Australia
Study Population: 6800 critically ill or
trauma victims who require at least one red
cell unit within the first 72 hrs of acute care.
The Study Intervention
Leukoreduced RBCs
‘Fresh’ RBCs defined as 8 days or less
 Primarily
for feasibility as limited biological
rationale for cut-off
Control group…standard-issue RBCs
(average age of 21 days)
Local transfusion guidelines/practices
ABLE…What Outcomes will we measure?
Primary outcome: 30-day all cause mortality.
Secondary outcomes:
1) Other mortality rates
2) Organ failure
3) Nosocomial infections
4) Quality of life using the SF-36 and costs
of care.
TRICC
Investigators
(Canada) [4]
North Thames
Blood Interest
Group (UK)
[5]
ABA
Multicenter
Trials Group
(US, Canada)
[6]
ABC Trial
(Western
Europe) [1]
CRIT Study
(USA) [2]
Trauma
patients from
CRIT Study
(USA) [3]
3534
4892
576
5298
1247
666
Mean admission
hemoglobin (g/dL)
11.3 ± 2.3
11.0 ± 2.4
11.1 ± 2.4
9.9 ± 2.2
--
--
Percentage of
patients transfused
in ICU
37.0%
44.1%
55.4%
25.0%
53.4%
74.7%
Mean transfusions
per patient (units)
4.8 ± 5.2
4.6 ± 4.9
5.8 ± 5.5
4.6 ± 6.7
5.7 ± 5.2
13.7 ± 1.1
Mean pretransfusion
hemoglobin (g/dL)
8.4 ± 1.3
8.6 ± 1.7
8.9 ± 1.8
8.6 ± 1.3
--
9.3 ± 0.1
Mean ICU length of
stay (days)
4.5
7.4 ± 7.3
9.4 ± 8.6
4.8 ± 12.6
--
--
ICU mortality
13.5%
13.0%
--
22.0%
21.5%
--
Hospital mortality
20.2%
17.6%
9.9%
--
--
21.0%
n
[1] Vincent JL, Baron JF, Reinhart K, et al. ABC (Anemia and Blood Transfusion in Critical Care ) Investigators. Anemia and blood transfusion in critically ill patients.
JAMA 2002;288:1499-1507.
[2] Corwin HL, Gettinger A, Pearl RG, et al. The CRIT Study: Anemia and blood transfusion in the critically ill – current clinical practice in the United States. Crit Care
Med 2004;32:39-52.
[3] Shapiro MJ, Gettinger A, Corwin H, Napolitano LM, Levy M, Abraham E, Fink MP, MacIntyre N, Pearl RG, Shabot MM. Anemia and blood transfusion in trauma
patients admitted to the intensive care unit. J Trauma 2003;55:269-274.
[4] Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requireemtns in
Critical Care investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340:409-417.
[5] Rao MP, Boralessa H, Morgan C, et al and the North Thames Blood Interest Group. Blood component use in critically ill patients. Anaesthesia 2002 Jun;57(6):530-4.
[6] Palmieri TL, Caruso DM, Foster KN, et al and the American Burn Association (ABA) Multicenter Trials Group. Effect of blood transfusion on outcome after major
burn injury: A multicenter study. Crit Care Med 2006 Jun;34(6):1602-7.
Guidelines for Transfusion in Trauma
Studies on RBC transfusion and outcome in ischemic heart disease.
Year
Hebert
Hebert
Wu
Blood Transfusion and Clinical
Study
Design
Patients
Primary Results
Increased survival with
transfusion when Hb < 9.5
g/dL
1997
Retrospective
Critically ill patients with
cardiac disease, as part of a
retrospective assessment of
transfusion practices in
Canadian ICUs
2001
Prospective,
subgroup
analysis
357
Subgroup of patients with
cardiac disease from the
TRICC trial
No difference in mortality
Increased organ dysfunction
with transfusion
Approx
79,000
Patients aged ≥64 years who
had been hospitalized with a
disgnosis of acute MI,
Medicare database
Increased survival with
transfusion
Approx
24,000
Meta-analysis of data that
had been collected as part of
the GUSTO IIb, PURSUIT and
PARAGON B trials of
patients with ACS
Increased mortality,
combined death or MI
Data from 16 ACS studies
Decreased mortality in STEMI
Increased mortality in nonST-elevation ACS
Patients with non-STsegment elevation acute
coronary syndromes
Increased mortality,
combined death or MI
2001
Retrospective
Rao
2004
Retrospective
Sabatine
2005
Retrospective
Yang
n
2005
Retrospective
85,111
total
cohort;
74,271 no
CABG
Adapted in part from: Gerber DR. Crit Care Med 2008;36(4):1068-1074.
Studies on RBC transfusion and outcome in ischemic heart disease.
Year
Singla
Aronson
2007
2008
Study
Design
n
Prospective
database
Prospective
database
2008
2358
Patients with anemia and
suspected ACS receiving
transfusion, using data
prospectively collected as
part of an ongoing registry
Increased mortality, recurrent
MI
Patients with acute MI
Decreased mortality in
patients with nadir Hb <
8g/dL
44242
CRUSADE
Initiative
Primary Results
Increased mortality in
patients with nadir Hb >
8g/dL
Prospective
database
Alexander
Patients
Patients with non-STsegment elevation acute
coronary syndromes
Increased mortality in
patients with nadir
Hematocrit > 30%
Decreased mortality in
patients with nadir
Hematocrit ≤ 24%
Adapted in part from: Gerber DR. Crit Care Med 2008;36(4):1068-1074.
FOCUS






NHLBI
Transfusion
Trigger for
Functional
Outcomes in
Cardiovascular
Patients
Undergoing
Surgical Hip
Fracture Repair
N=2600
25 Med Ctrs
US, Canada
J.L. Carson MD
FOCUS

Inclusion criteria:
– Undergo surgery for hip fracture
– Have a history of cardiovascular disease
– Have a postoperative Hgb < 10 g/dL







Randomized to keep Hgb > 10 g/dL or not
Tx permitted but not required if Hgb < 8 g/dL
Primary outcome is ability to walk 10 feet without human
assistance at 60 days
Negative outcome is postoperative unstable angina, myocardial
infarction or death
MI diagnosis based on 4 blood tests, 3 EKGs, medical history
Telephoned at 30 and 60 days to determine functional capacity
and vital status.
Long-term mortality by searching vital statistics registries in
U.S. and Canada
State of the Science Symposium in Transfusion
Medicine and Hemostasis/Thrombosis

SURGERY Committee

Jeff Carson (Chair) Clinical trials and Transfusion Medicine,
Robert Wood Johnson Medical School

Darrell Triulizi (Co-Chair) Transfusion Medicine, University of
Pittsburgh

John Marshall: General Surgery, Univ. Toronto

Lena Napolitano: General Surgery, Univ. Michigan

Chris Stowell: Transfusion Medicine, Mass General

Richard Weiskopf: Anesthesia, UCSF

Transfusion Triggers in CAD, Elective Cardiac Surgery
Effect of Blood
Transfusion on LongTerm Survival
After Cardiac
Operation
•
•
1915 CABG pts
After correction for
comorbidities and
other factors, tx was
still associated with
a 70% increase in
mortality (RR 1.7;
95% CI 1.4 to 2.0; p
0.001).
Engoren MC et al. (MCO, Toledo)
Ann Thorac Surg 2002;74:1180–6
•
•
•
10,289 CABG pts, 1995 – 2002
Perioperative RBC tx is
associated with adverse
outcome.
Attention should be directed
toward blood conservation
methods and a more
judicious use of PRBC.
Cleveland Clinic, OH
0
1
2
3-5
≥6
Ann Thorac Surg 2006;81:1650 –7
• Institution-specific protocols should screen for patients at high risk for blood
transfusion. Available evidence-based blood conservation techniques include:
– (1) drugs that increase preoperative blood volume (eg, erythropoietin) or decrease
postoperative bleeding (eg, antifibrinolytics)
– (2) devices that conserve blood (eg, intraoperative blood salvage and blood sparing
interventions)
– (3) interventions that protect the patient’s own blood from the stress of operation (eg,
autologous predonation and normovolemic hemodilution)
– (4) consensus, institution-specific blood transfusion algorithms supplemented with pointof-care testing, and most importantly
– (5) a multimodality approach to blood conservation combining all of the above
Society of Thoracic Surgeons Blood Conservation Guideline Task Force; Society of Cardiovascular
Anesthesiologists Special task Force on Blood Transfusion. Ann Thorac Surg 2007;83:S27-86.
Do Blood Transfusions
Improve Outcome
in Sepsis?
Efficacy of Blood Tx in Sepsis
Zimmerman JL. Use of blood products in sepsis: An evidence-based review. Crit Care
Med 2004;32[Suppl]S542-547
Changes in measurements of post-transfusion
Author and Year
Study population
N
Amount transfused
(units)
↑ Hb
↑ DO2
↑ VO2
↓ Lactate
Ronco et al 1990
PCP pneumonia
5
1.5 Units
Yes
Yes
Yes
NA
Fenwick et al 1990
ARDS
24
1.5 Units
Yes
Yes
No
No
Ronco et al 1991
ARDS
17
1.5 Units
Yes
Yes
No
NA
Shah et al 1982
Post-trauma
8
1 or 2 Units
Yes
No
No
NA
Steffes et al 1991
Postoperative and Post-trauma
21
1-2 Units
Yes
Yes
Yes
No
Babineau et al 1992
Postoperative
31
328 ± 9 mL
Yes
Yes
No
No
Gilbert et al 1988
Septic
17
∆ 20 g/L
Yes
Yes
No
No
Dietrich et al 1990
Medical shock (septic/cardiac)
32
577 mL
Yes
Yes
No
No
Conrad et al 1990
Septic shock
19
∆ 30 g/L
Yes
Yes
No
No
Marik et al 1993
Septic
23
3 Units
Yes
Yes
No
No
Lorento et al 1993
Septic
16
2 Units
Yes
Yes
No
NA
Mink et al 1990
Septic shock
2 mo – 6 y
8
8-10 mL/kg x 1-2 h
Yes
Yes
No
NA
Lucking et al 1990
Septic shock
4 mo – 15 y
7
10-15 mL/kg x 1-3 h
Yes
Yes
Yes
NA
Silverman et al 1992
Septic shock
21 – 88 y
21
2 Units
Yes
Yes
No
No
Gramm et al 1996
Septic shock
46 ± 3 y
19
2 Units
Yes
No
No
NA
Fernandes et al 2001
Septic shock
18-80y
10
1 Units
Yes
No
No
No
Kahn et al 1986
Acute respiratory failure
15
7-10 mL/kg
Yes
No
No
NA
Casutt et al 1999
Postoperative
32-81y
67
368 ± 10 mL
Yes
Yes
No
NA
Walsh et al 2004
Euvolemic anemic critically ill
patients without ongoing
hemorrhage
22
2 Units
Yes
NA
NA
No
Mazza et al 2005
SIRS/Sepsis
29
1-3 Units
Yes
NA
NA
No
Early Goal-directed Therapy in the Rx of
Severe Sepsis and Septic Shock
•
•
Severe sepsis and septic shock patients (n=263)
–
SIRS and SBP < 90mm Hg or lactate > 4mmol/L
–
Prospective, randomized controlled trial
–
Goal-directed therapy vs. control (standard of care)
Goal-directed therapy performed in ER prior to ICU
–
Placement of oximetric CVP line, CVP goal 8-12, ScVO2 > 70%
–
Guidelines for pressor and vasodilators, dobutamine, blood tx
–
Maintained for at least 6 hours
Rivers E et al. NEJM 345(19) November 8, 2001:1368-77
Early Goal-directed Therapy in the Rx of
Severe Sepsis and Septic Shock
•
•
Early Goal-directed Therapy resulted in:
Reduced In-hospital mortality, 30.5% vs 46.5%
(p=0.0009)
•
•
Higher ScVO2, lower lactate, lower base deficit
Early goal-directed therapy provides significant
benefits in outcome in patients with severe sepsis
and septic shock.
Rivers E et al. NEJM 345(19) November 8, 2001:1368-77
Validation Study
Multicenter Trial
20 sites
Derek Angus et al.
Univ. of Pittsburgh
ProCESS
Protocolized Care for
Early Septic Shock
NIH-sponsored
$8.4 Million
EAST/SCCM Blood Tx Guidelines
•
•
•
•
•
Recommendations Regarding RBC Transfusion
in Sepsis
Level 1
There are insufficient data to support Level 1
recommendations on this topic.
Level 2
The transfusion needs for each septic patient must
be assessed individually since optimal transfusion
triggers in sepsis patients are not known and there
is no clear evidence that blood transfusion
increases tissue oxygenation.
Anemia of
Chronic
Disease or
“Anemia of
Inflammation”



Dysregulation of
iron homeostasis
Impaired
proliferation of
erythroid progenitor
cells
Blunted EPO
response
Weiss and Goodnough.
N Engl J Med.
2005;352(10):1011-1023.
Blunted Epo Response in Critically Ill
Inhibition of EPO gene transcription in
renal juxtaglomerular cells
Inflammatory Cytokines
(IL-1, IFN, TNF, TGF)
Direct inhibition of RBC
production by bone marrow
Direct inhibition of the erythroid
precursor cell response to
erythropoietin
Indirect limitation of iron availability by
increasing iron sequestration in macrophages.
SICU - Patient Characteristics
2004
2005
2006
2007
2008
n
1491
1361
1353
1354
1275
APACHE III Score-Day 1
48.2
48.3
49.1
50.5
55.8
Hospital LOS
14.1
14
13.9
12.9
13.5
ICU-LOS
4.1
4.76
4.77
4.22
4.49
Readmissions Rates
6.2
7.9
7.1
8.4
7.4
Active Treatment
56%
51%
57%
63%
64%
Low-Risk Monitor
34%
38%
33%
27%
24%
Level of Therapy on Admission
Anemia Management Protocol
SICU Epoetin Blood Study: Anemia Patients
12.0
10.0
Yes_Epoetin Avg RBC Units
8.0
6.0
4.0
2.0
40% Reduction in Blood Tx in SICU
0.0
Oct - Dec 04 Cases:
Pre-Protocol Period
Oct-Dec 2004
Jun - Aug 05 Cases: PreProtocol Period
Oct - Dec 05 Cases
Protocol Period
Apr - June 06 Cases
Protocol Period
Jul - Sep 06 Cases
Protocol Period
Jul-Sep 2006
SICU Blood Utilization
Added to Keystone ICU Reports
Oct-Dec 2004
Jul-Sep 2006
SICU Blood Utilization
Added to Keystone ICU Reports
Oct-Dec 2004
Jul-Sep 2006
IC U M o rt a lit y R a t e s C o m pa re d t o
N a t io na l & S im ila r Ins t it ut io ns R a t e s
ICU Mortality
8
6
M o rtality
Rate %
4
2
0
2004
2005
2006
2007
A ctual %
5.1
3.64
3.73
Natio nal %
6.6
6.14
6.06
Similar %
7.2
6.72
6.67
3.36%
6.60%
7.21%
0.47
0.41
O/E
0.71
0.54
Hospital Mortality
H o s pit a l M o rt a lit y R a t e s C o m pa re d t o
N a t io na l & S im ila r Ins t it ut io ns R a t e s
15
M o rtality
Rate %
10
5
0
2004
2005
2006
2007
A ctual%
7.32
5.63
5.95
Natio nal %
10.4
9.72
9.88
5.35%
10.89%
Similar %
9.16
8.54
8.78
9.67%
0.74
0.59
0.55
0.56
O/E
Blood Dashboard for Clinical Services - DRAFT
Trend Report of Percent of RBC
Transfusions by Pre-Transfusion Hct
Current Month “Snapshot” of
Percent of RBC Transfusions by PreTransfusion Hct with “drill-down” to
Patient-Level Detail
Summary

Anemia is common

No evidence that blood tx for treatment of
anemia improves outcome

Critically ill patients can tolerate Hb levels
as low as 7 mg/dL

Blood should be transfused for physiologic
indications

New UMich Blood Tx Guidelines
UM Carelink Support for Improved
Transfusion Practice
Andrew Rosenberg MD
Medical Director, UM Carelink
Chief, Critical Care Division Anesthesiology
Clinical IT supports good decisions, best
practices & institution policies
• For emergency transfusion call Blood Bank
• Pre-op requests for PRBCs on standby & OR
transfusion NOT part of this process.
• UMCL (UM Carelink);
– Is the primary method to order blood.
– Provides Clinical Decision Support {Alerts}
– Serves as a useful clinical database {Queries}
• Clinician feedback needed (6-2222, light bulb
icon in UMCL)
Transfusion Alert Rule Logic
• Based on ECCA Transfusion Guidelines
– Hemodynamically stable anemia w/out CAD


Transfusion trigger= Hg < 7g/dL
Maintain Hg 7-9g/dL
• For PRBC Order set only
–
–
–
–
1 or 2 units ordered (alert will NOT fire for 3 or more units)
And Hemoglobin > 7g/dL
And/or Hg result >48 hrs old/ Or no Hg result available
And Pt age > 17 yo.
Alert Box Information
Four Alert Messages
I. Hgb <7 g/dL but last Hgb result > 48 hours.
• Request does not meet ECCA Guidelines when ordering 1 or 2 units PRBC
• Last HGB is over 48 hours old
• HGB: ## g/dL DATE
• Confirm HGB before ordering or select override reason to complete order.
II. Hgb> 7g/dL and HGB result < 48 hrs.
• Transfusion may not be advised if the HGB is > 7g/dL
III. Hbg > 7 g/dL but HGB result > 48 hrs.
• HGB is greater than 7 g/dL and is over 48 hours old.
IV. No Hgb result available
• No HGB result on file
Override Reasons
1.
2.
3.
4.
5.
6.
7.
8.
Active Bleeding
Cardiovascular disease
Hemoglobinopathy
Hemolysis
Oxygen carrying deficit
Refractory Hypotension
Symptomatic anemia
Attending Physician deems necessary
UMHS – Blood Transfusion Guideline
Order & Compliance Monitoring (Future State Map)
Blood Transfusion Guideline
*RBC Transfusion Trigger = Hemoglobin < 7
Annual
Review
Evidence
Based
Compliance
Report Capture
(If Order Is
Beyond Trigger)
Blood
Transfusion
Ordered
House Wide
Communication/
Education
Carelink Order
“Checkpoints”
*Redefines role/scope of
Transfusion Committee to
act as oversight body
*Reports Track Compliance To
Guideline & Transfusion Volume
Email Sent
To Service
Chief
*Email includes link to patient
level data to assist review
Response
Explanation
Submitted To
Transfusion
Committee
Response
Review By
Transfusion
Committee