Blood Transfusion: New Guidelines

Blood Transfusion: Blood Transfusion: New GuidelinesNew Guidelines

Joint Surgery and Anesthesiology Grand RoundsJuly 2, 2009

Paul Picton MDLena M. Napolitano MDAndrew 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

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

TRICC - Design

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

The TRICC Study

Herbert PC, et al. NEJM 1999

8.7% vs 16.1% 5.7% vs 13.0%

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

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

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

• 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

Rao SV et al. JAMA. 2004;292:1555-1562

Transfusion

No Transfusion

Adjusted hazard ratio

3.94(3.26-4.75)

• 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

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)

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)

$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

$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

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 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

Adult Blood Transfusion Adult Blood Transfusion Clinical GuidelinesClinical Guidelines

Plan and Guideline endorsed by ECCA on March 24, 2009

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

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

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.

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

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

Risks of Blood TransfusionRisks of Blood Transfusion

Viral transmission

Acute transfusion reactions

Immunosuppression

Acute inflammatory response

Noninfectious Hazards Immunosuppression Infection

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

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.

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%

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

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

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

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

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

Gould S et al. Am J Crit Care; Jan 2007;16(1):39-48

Why is blood transfusionWhy is blood transfusionNOT associated withNOT associated withimproved outcome?improved outcome?

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

Age of BloodAge of Blood

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.

Schechter, Gladwin, NEJM April 10, 2003

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

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 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).

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 patientsInternational Study, CIHR, NIH, othersProjected 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 rates2) Organ failure3) Nosocomial infections4) Quality of life using the SF-36 and costs of care.

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.

Guidelines for Transfusion in TraumaGuidelines for Transfusion in Trauma

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.

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.

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

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

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

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

• 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

• 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.

Do Blood TransfusionsDo Blood TransfusionsImprove OutcomeImprove Outcome

in Sepsis?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

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

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 StudyMulticenter Trial

20 sitesDerek Angus et al.Univ. of Pittsburgh

ProCESSProtocolized Care for

Early Septic ShockNIH-sponsored

$8.4 Million

• 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

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.

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.

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%

Anemia Management ProtocolAnemia Management Protocol

40% Reduction in Blood Tx in SICU

Oct-Dec 2004 Jul-Sep 2006

SICU Blood UtilizationSICU Blood Utilization

Oct-Dec 2004 Jul-Sep 2006

Added to Keystone ICU Reports

SICU Blood UtilizationSICU Blood Utilization

Oct-Dec 2004 Jul-Sep 2006

Added to Keystone ICU Reports

ICU Mortality

O/E 0.71 0.54 0.47 0.41

3.36%

2007

6.60%7.21%

Hospital Mortality

O/E 0.74 0.59 0.55 0.56

5.35%

2007

10.89%

9.67%

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

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

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. Active Bleeding

2. Cardiovascular disease

3. Hemoglobinopathy

4. Hemolysis

5. Oxygen carrying deficit

6. Refractory Hypotension

7. Symptomatic anemia

8. Attending Physician deems necessary

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)