blood transfusion: new guidelines joint surgery and anesthesiology grand rounds july 2, 2009 paul...
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![Page 1: Blood Transfusion: New Guidelines Joint Surgery and Anesthesiology Grand Rounds July 2, 2009 Paul Picton MD Lena M. Napolitano MD Andrew Rosenberg MD](https://reader030.vdocuments.mx/reader030/viewer/2022032800/56649d2b5503460f949fff92/html5/thumbnails/1.jpg)
Blood Transfusion: Blood Transfusion: New GuidelinesNew Guidelines
Joint Surgery and Anesthesiology Grand RoundsJuly 2, 2009
Paul Picton MDLena M. Napolitano MDAndrew Rosenberg MD
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Perioperative Transfusion Triggers
Paul Picton MD MRCP FRCA
Assistant Professor
Director, Transplant Anesthesia
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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
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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
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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
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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
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The TRICC Study
Herbert PC, et al. NEJM 1999
• 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
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TRICC - Design
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The TRICC Study
Herbert PC, et al. NEJM 1999
No difference 30 day mortality
In “healthy” (APACHE II < 20) and young (<55yrs) patientsTransfusion increased mortality
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The TRICC Study
Herbert PC, et al. NEJM 1999
8.7% vs 16.1% 5.7% vs 13.0%
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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)
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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
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“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.”
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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
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CRIT Results
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
35% of Blood transfused in patients with Hgb 9
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Hematocrit versus Postop Morbidity & Ischemia
0
20
40
60
80
100
23-25 26-28 29-31 32-34 35-37
Hematocrit (%)
Per
cen
t o
f P
atie
nts
Nelson A, Fleischer L, et al. Crit Care Med 1993
ST Sx
n = 27 high-risk pts undergoing infra-inguinal
arterial bypass
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• 2001
• Retrospective cohort
• Cooperative Cardiovascular Project
• 78,974 patients ≥ 65 yrs acute MI
• 30 day mortality
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Blood transfusion associated with ↓ mortality if Hct < 30%
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• 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
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Blood Transfusion and Clinical Outcome in Acute Coronary Syndrome
Rao SV et al. JAMA. 2004;292:1555-1562
Transfusion
No Transfusion
Adjusted hazard ratio
3.94(3.26-4.75)
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• 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
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Results
Crit Care Med 2008;36(9):2667-74
Association between blood transfusion and the risk of death (OR & 95% CI). Pooled OR 1.7 (95% CI 1.4-1.9)
Association between blood transfusion and the risk of infectious complications (OR & 95% CI). Pooled OR 1.8 (95% CI 1.5-2.2)
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Results
Crit Care Med 2008;36(9):2667-74
Association between blood transfusion and the risk of ARDS (OR & 95% CI).
Pooled OR 2.5 (95% CI 1.6-3.3)
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$11.08 $10.76
$12.56 $12.56
$14.97
$0
$5
$10
$15
$20
FY'04 FY'05 FY'06 FY'07 FY'08
UMHHC direct cost of bloodproducts
Financial BurdenM
illio
ns
Based on data from UMHHC cost accounting system.Cost includes cost of blood products and allocatedcosts of labor
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$553 $534
$602 $590
$696
$0
$200
$400
$600
$800
$1,000
FY'04 FY'05 FY'06 FY'07 FY'08
Cost per case
44% 43% 44% 46% 47%
0
20
40
60
80
100
FY'04 FY'05 FY'06 FY'07 FY'08
% of cases using blood
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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.
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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
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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
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Univ. Michigan Adult Blood Univ. Michigan Adult Blood Transfusion Guidelines: 2009 Transfusion Guidelines: 2009
Lena M. Napolitano MD, FACS, FCCP, FCCMProfessor of Surgery
Division Chief, Acute Care SurgeryDepartment of SurgeryUniversity of Michigan
Ann Arbor, MI
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Adult Blood Transfusion Adult Blood Transfusion Clinical GuidelinesClinical Guidelines
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Plan and Guideline endorsed by ECCA on March 24, 2009
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Project Overview & Scope Of Work
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
Blood Utilization lean project work was commissioned by both OCA & Hospital Administration, under the oversight of Dr. Skip Campbell
Team Make-Up
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
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Guidelines for Blood Guidelines for Blood Transfusion: PRBCsTransfusion: PRBCs
These guidelines are intended to ensure that the most These guidelines are intended to ensure that the most appropriate, efficient and safe use of the blood supply is appropriate, efficient and safe use of the blood supply is achievedachieved
To establish evidence-based criteria for the transfusion of To establish evidence-based criteria for the transfusion of blood componentsblood components
Every indication for the use of blood products cannot be Every indication for the use of blood products cannot be anticipatedanticipated
These guidelines are not intended to override physician These guidelines are not intended to override physician judgementjudgement
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Guidelines for Blood Guidelines for Blood Transfusion: PRBCsTransfusion: PRBCs
Hemodynamically stable anemia without acute coronary syndrome: Hemodynamically stable anemia without acute coronary syndrome: hemoglobin trigger less than 7 g/dLhemoglobin trigger less than 7 g/dL, with a transfusion goal to , with a transfusion goal to maintain hemoglobin 7 – 9 g/dL.maintain hemoglobin 7 – 9 g/dL.
Acute hemorrhage with evidence of hemodynamic instability or Acute hemorrhage with evidence of hemodynamic instability or inadequate oxygen delivery inadequate oxygen delivery
Symptomatic (tachycardia, tachypnea, postural hypotension) anemia (Hb Symptomatic (tachycardia, tachypnea, postural hypotension) anemia (Hb < 10 g/dL) not explained by other causes < 10 g/dL) not explained by other causes
Chronic Tx-dependent bone marrow syndromes: Hb < 10 g/dL.Chronic Tx-dependent bone marrow syndromes: Hb < 10 g/dL.
Transfusion or exchange transfusion for severe sickle syndromes. Transfusion or exchange transfusion for severe sickle syndromes.
Hemodynamically stable anemia with ischemic heart disease: current Hemodynamically stable anemia with ischemic heart disease: current evidence does not support routine transfusion in non-ST segment evidence does not support routine transfusion in non-ST segment elevation acute coronary syndromes; although in ST-segment elevation elevation acute coronary syndromes; although in ST-segment elevation myocardial infarction Tx may be beneficial. myocardial infarction Tx may be beneficial.
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RBCs should be administered as RBCs should be administered as single unitssingle units for most operative for most operative and inpatient indications (transfuse and reassess strategy) except and inpatient indications (transfuse and reassess strategy) except for ongoing blood loss with hemodynamic instability.for ongoing blood loss with hemodynamic instability.
Tx decisions are clinical judgments that should be based on the Tx decisions are clinical judgments that should be based on the overall clinical assessment of the individual patient. Transfusion overall clinical assessment of the individual patient. Transfusion decisions should not be based on laboratory parameters alone. decisions should not be based on laboratory parameters alone.
Routine premedication is Routine premedication is notnot advised unless the patient has a advised unless the patient has a history of previous transfusion reactions. Premedication has not history of previous transfusion reactions. Premedication has not been shown to reduce the risk of transfusion reactions.been shown to reduce the risk of transfusion reactions.
Guidelines for Blood Guidelines for Blood Transfusion: PRBCsTransfusion: PRBCs
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EAST / SCCM Blood Tx GuidelinesEAST / SCCM Blood Tx GuidelinesCLINICAL 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
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
In press.November 2009Crit Care Med
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Risks of Blood TransfusionRisks of Blood Transfusion
Viral transmission
Acute transfusion reactions
Immunosuppression
Acute inflammatory response
Noninfectious Hazards Immunosuppression Infection
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Decline in HIV, HBV, HCV Risks Decline in HIV, HBV, HCV Risks of Transmission via Blood Txof Transmission via Blood Tx
Busch MP, et al. JAMA. 2003;289:959-62.
Ris
k o
f In
fect
ion
per
R
isk
of
Infe
ctio
n p
er
Un
it T
ran
sfu
sed
Un
it T
ran
sfu
sed
1:100
1:1000
1:10,000
1:100,000
1:1,000,000
1:10,000,0001983 1985 1987 1989 1991 1993 1995 1997 1999
2001YearYear
Revised DonorDeferral Criteria
Non-A, Non-B Hepatitis
Surrogate Testing
HIV AntibodyScreening
HCV AntibodyScreening
p24 AntigenTesting
HCV and HIVNucleic Acid
Testing
HIVHCV
HBV
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Risks of Transfusion: Risks of Transfusion: Infectious DiseaseInfectious 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.
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Williamson LM, et al. BMJ. 1999;319:16-9.
Serious Hazards of TransfusionSerious Hazards of Transfusion
Based on 366 spontaneously-reportedBased on 366 spontaneously-reporteddeaths/major complications between deaths/major complications between October 1996 and September 1998 October 1996 and September 1998 in the UK and Ireland.in the UK and Ireland.
Transfusion-transmitted Transfusion-transmitted infectionsinfections
Acute lung injuryAcute lung injury
Post-transfusionPost-transfusionpurpurapurpura
Graft vs hostGraft vs hostdiseasedisease
DelayedDelayedtransfusiontransfusion
reactionreaction
AcuteAcutetransfusiontransfusion
reactionreaction
Incorrect blood/Incorrect blood/componentcomponenttransfusedtransfused
3%3%
6%6%
8%2%
14%
15%
53%
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Risks of Blood TransfusionRisks of Blood TransfusionMinor allergic reactions
Bacterial infection (platelets)
Viral hepatitis
Hemolytic transfusion reaction
HTLV I/II infection
Acute lung injury
Anaphylactic shock
Fatal hemolytic reaction
Graft-vs-host disease
Immunosuppression
1:100
1:2,500
1:5,000
1:6,000
1:200,000
1:500,000
1:500,000
1:600,000
Rare
Unknown
HTLV = human T-cell leukemia-lymphoma virus.Klein HG. Am J Surg. 1995. 170;6A(suppl):21S-26S.
TRALI 1:5,000
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Immune Effects of BloodImmune 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
McAlister FA, et al, British Journal of Surgery 1998; 85: 171-178Innerhofer et al. Transfusion 1999 Oct;39(10):1089
TRIM – Transfusion-associated Immunomodulation
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Blood Tx Increases Risk of Blood Tx Increases Risk of Postoperative Bacterial InfectionPostoperative 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
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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
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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
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Reed W, et al. Semin Hematol 2007:44:24-31Utter G et al. Transfusion 2006 Nov;46(11):1863-9
Leukoreduction does not diminish tx-associated Microchimerism
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Gould S et al. Am J Crit Care; Jan 2007;16(1):39-48
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Why is blood transfusionWhy is blood transfusionNOT associated withNOT associated withimproved outcome?improved outcome?
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Stored RBCsStored 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
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Age of BloodAge of Blood
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Poor Efficacy of Blood TxPoor 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.
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Schechter, Gladwin, NEJM April 10, 2003
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Distribution of Transfused Units by Age of Blood – CRIT Study
0%
5%
10%
15%
20%
25%
30%
35%
Pe
rce
nta
ge
of
Pa
tie
nts
Oldest Age of Blood in Days
0 - 10 10 - 20 20 - 30 30 - 40 > 40
60% of Blood transfused is > 20 days old
In Trauma Subset, 68% of blood is > 20 days old
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March 20, 2008
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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 in-hospital 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).
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Composite Outcome:
In-hospital mortality
And Complications (STS)
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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 patientsInternational Study, CIHR, NIH, othersProjected n = 6800
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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.
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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
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ABLE…What Outcomes will we measure?
Primary outcome: 30-day all cause mortality.
Secondary outcomes:1) Other mortality rates2) Organ failure3) Nosocomial infections4) Quality of life using the SF-36 and costs of care.
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ABC Trial(Western
Europe) [1]
CRIT Study(USA) [2]
Trauma patients from CRIT Study
(USA) [3]
TRICC Investigators(Canada) [4]
North Thames Blood Interest Group (UK) [5]
ABA Multicenter
Trials Group (US, Canada)
[6]
n 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 pre-transfusion 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%
[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.
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Guidelines for Transfusion in TraumaGuidelines for Transfusion in Trauma
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Blood Transfusion and ClinicalBlood Transfusion and ClinicalStudies on RBC transfusion and outcome in ischemic heart disease.
YearStudy
Designn Patients Primary Results
Hebert 1997 Retrospective
Critically ill patients with cardiac disease, as part of a retrospective assessment of
transfusion practices in Canadian ICUs
Increased survival with transfusion when Hb < 9.5
g/dL
Hebert 2001Prospective,
subgroup analysis
357Subgroup of patients with cardiac disease from the
TRICC trial
No difference in mortalityIncreased organ dysfunction
with transfusion
Wu 2001 RetrospectiveApprox 79,000
Patients aged ≥64 years who had been hospitalized with a
disgnosis of acute MI, Medicare database
Increased survival with transfusion
Rao 2004 RetrospectiveApprox 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
Sabatine 2005 Retrospective Data from 16 ACS studiesDecreased mortality in STEMI
Increased mortality in non-ST-elevation ACS
Yang 2005 Retrospective
85,111 total
cohort;74,271 no
CABG
Patients with non-ST-segment elevation acute
coronary syndromes
Increased mortality, combined death or MI
Adapted in part from: Gerber DR. Crit Care Med 2008;36(4):1068-1074.
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Studies on RBC transfusion and outcome in ischemic heart disease.
YearStudy
Designn Patients Primary Results
Singla 2007Prospective
database
Patients with anemia and suspected ACS receiving transfusion, using data
prospectively collected as part of an ongoing registry
Increased mortality, recurrent MI
Aronson 2008Prospective
database2358 Patients with acute MI
Increased mortality in patients with nadir Hb >
8g/dL
Decreased mortality in patients with nadir Hb <
8g/dL
Alexander 2008
Prospective database
CRUSADE Initiative
44242Patients with non-ST-
segment 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.
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FOCUSFOCUS 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
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FOCUSFOCUS 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
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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
State of the Science Symposium in Transfusion
Medicine and Hemostasis/Thrombosis
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Effect of Blood Transfusion on Long-Term SurvivalAfter 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
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• 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.
Ann Thorac Surg 2006;81:1650 –7
0123-5≥ 6
Cleveland Clinic, OH
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• 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 point-of-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.
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Do Blood TransfusionsDo Blood TransfusionsImprove OutcomeImprove Outcome
in Sepsis?in Sepsis?
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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
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Author and Year Study population NAmount transfused
(units)
Changes in measurements of post-transfusion
↑ 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 1990Septic shock2 mo – 6 y
8 8-10 mL/kg x 1-2 h Yes Yes No NA
Lucking et al 1990Septic shock4 mo – 15 y
7 10-15 mL/kg x 1-3 h Yes Yes Yes NA
Silverman et al 1992Septic shock
21 – 88 y21 2 Units Yes Yes No No
Gramm et al 1996Septic shock
46 ± 3 y19 2 Units Yes No No NA
Fernandes et al 2001Septic shock
18-80y10 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 1999Postoperative
32-81y67 368 ± 10 mL Yes Yes No NA
Walsh et al 2004Euvolemic 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
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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
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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
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Validation StudyMulticenter Trial
20 sitesDerek Angus et al.Univ. of Pittsburgh
ProCESSProtocolized Care for
Early Septic ShockNIH-sponsored
$8.4 Million
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• 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.
EAST/SCCM Blood Tx Guidelines
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Anemia of Anemia of Chronic Chronic
Disease orDisease or“Anemia of “Anemia of
Inflammation”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.
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Blunted Epo Response in Critically IllBlunted Epo Response in Critically Ill
Inflammatory Cytokines(IL-1, IFN, TNF, TGF)
Inhibition of EPO gene transcription in renal juxtaglomerular cells
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.
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SICU - Patient CharacteristicsSICU - 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
Level of Therapy on Admission
Active Treatment 56% 51% 57% 63% 64%
Low-Risk Monitor 34% 38% 33% 27% 24%
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Anemia Management ProtocolAnemia Management Protocol
40% Reduction in Blood Tx in SICU
Oct-Dec 2004 Jul-Sep 2006
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SICU Blood UtilizationSICU Blood Utilization
Oct-Dec 2004 Jul-Sep 2006
Added to Keystone ICU Reports
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SICU Blood UtilizationSICU Blood Utilization
Oct-Dec 2004 Jul-Sep 2006
Added to Keystone ICU Reports
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ICU Mortality
O/E 0.71 0.54 0.47 0.41
3.36%
2007
6.60%7.21%
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Hospital Mortality
O/E 0.74 0.59 0.55 0.56
5.35%
2007
10.89%
9.67%
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Trend Report of Percent of RBC Transfusions by Pre-Transfusion Hct
Current Month “Snapshot” of Percent of RBC Transfusions by Pre-Transfusion Hct with “drill-down” to
Patient-Level Detail
Blood Dashboard for Clinical Services - DRAFT
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SummarySummary
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
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UM Carelink Support for Improved Transfusion Practice
Andrew Rosenberg MD
Medical Director, UM Carelink
Chief, Critical Care Division Anesthesiology
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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)
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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.
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Alert Box Information
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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
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Override Reasons
1. Active Bleeding
2. Cardiovascular disease
3. Hemoglobinopathy
4. Hemolysis
5. Oxygen carrying deficit
6. Refractory Hypotension
7. Symptomatic anemia
8. Attending Physician deems necessary
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Blood Transfusion
Ordered
Compliance Report Capture
(If Order Is Beyond Trigger)
Email Sent To Service
Chief
Response Explanation
Submitted To Transfusion Committee
Response Review By Transfusion Committee
Evidence Based
Carelink Order “Checkpoints”
House Wide Communication/
Education
Annual Review
Blood Transfusion Guideline
*Reports Track Compliance To Guideline & Transfusion Volume
*Email includes link to patient level data to assist review
*Redefines role/scope of Transfusion Committee to
act as oversight body
*RBC Transfusion Trigger = Hemoglobin < 7
UMHS – Blood Transfusion Guideline
Order & Compliance Monitoring (Future State Map)
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