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Surgical Bleeding and Transfusions: The Issues in 2004. Aryeh Shander, MD, FCCM, FCCP. Chief, Dept of Anesthesiology, Critical Care and Hyperbaric Medicine Englewood Hospital & Medical Center and Associate Clinical Professor, Mount Sinai School of Medicine. Objectives.

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Surgical bleeding and transfusions the issues in 2004

Surgical Bleeding and Transfusions: The Issues in 2004

Aryeh Shander, MD,FCCM, FCCP

Chief, Dept of Anesthesiology, Critical Care and Hyperbaric Medicine Englewood Hospital & Medical Center andAssociate Clinical Professor, Mount Sinai School of Medicine


Objectives
Objectives

  • Risks of bleeding, subsequent hypovolemia, and acute anemia

    • Compensatory mechanisms

      • Macrocirculation

      • Microcirculation

    • Morbidity & mortality

  • Risks of transfusions


Surgical bleeding

Vessel interruption

Bleeding stops

Delay in repair

Surgical repair

Bleeding contained

No need for further action

Surgical repair

Clotting

Factor consumption

Impaired clotting

Transfusion of

blood products

SIRS

Transfusion related

complications

Surgical Bleeding


Consequences of untreated hypovolemia
Consequences of untreated Hypovolemia

  • American College of Surgeons (ACS)

  • Advance Trauma Life Support (ATLS)

  • Society of Critical Care Medicine (SCCM)

Failure of the circulatory system

to maintain adequate cellular perfusion


Bleeding and hemorrhage
Bleeding and Hemorrhage

  • Macrocirculation

    • Compensation

    • Shifting of blood flow

  • Microcirculatory response

    • Cellular adaptation

    • Phenotype survival

SIR


MACROCIRCULATION

PLASMA

MICROCIRCULATION


Human Hemorrhage

and Blood Pressure

25-30% bleed

(n=6)

Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81


Human Hemorrhage

and Heart Rate

25-30% bleed

(n=6)

Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81


Human Hemorrhage

and Gastric Perfusion

p=0.002

25-30% bleed

(n=6)

Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81


“Fluid” + Dobutamine / High Risk Surgery

  • Deliberate perioperative increase of DO2 >600 ml/min/m2 using volume loading and dopexamine in RCT

  • Protocol (dopexamine) group had higher DO2 preop and postop (p<0.001)

Boyd O. JAMA 1993;270:2699-2707.


“Fluid” + Dobutamine / High Risk Surgery

%

*

*

* p<0.05

Lobo et al, Crit Care Med 2000;28:3396-3404.


Surgery trauma and the inflammatory response
Surgery, trauma and the inflammatory response

  • Surgical trauma: hyperinflammation versus immunosuppression? Menger MD, Vollmar B.Langenbecks Arch Surg 2004;389:475-84.

    • Surgery Vs. Trauma effect on ICAM and VCAM

    • Local (surgery) Vs. Systemic (trauma) Pro and inflammatory response

  • The role of interleukin-10 in the regulation of the systemic inflammatory response following trauma-hemorrhage Schneider CP et al, Biochim Biophys Acta 2004;1689:22-32.

    • Protective role

    • Damaging role



Anemia in cvd
Anemia in CVD

  • Hgb =  Mortality in CVD

    Carson/Gould – 300 Pts with Hgb <8 gm/dL - Stratified

    Carson JL et al, Lancet 1996;348:1055-60

  • Hgb < 9.5 g/dL = high risk with CVD

    • Hebert PC at al, Am J Respir Crit Care Med 1997;155:1618-23

  • Hgb < 7.0 g/dL acceptable with normal coronary circulation


Low hct and adverse outcome
Low Hct and Adverse Outcome

  • Lowest CPB HCT of <14% in low risk patients and <17% in high risk patients associated with doubling of mortality risk (Fang WC, Circulation 1997)

  • Below 23%, CPB HCT is inversely related to mortality (Defoe GR, Ann Thorac Surg 2001)

  • In postop cardiac surgical pts, inverse relationship exists between hemoglobin and major morbidity (Hardy JF, Br J Anaesth 1998)

  • Perioperative vital organ dysfunction, short- and intermediate-term mortality increased with lowest HCT <22% (Habib RH, J Thorac Cardiovasc Surg 2003)


Blood transfusion in Elderly Patients with Acute Myocardial InfarctionWu WC et al, NEJM 2001;345:1230-36

  • Cooperative Cardiovascular Project

    • 234,769 total patients 78,974 (33.6%) included

    • CMS ICD-9 discharge code for MI and anemia

    • Anemia – WHO definition Hct of 39% or less

    • Hct in the first 24 hrs

    • 30 day mortality

  • 3324 (4.2%) had Hct less than 30%

    • These patients had more trauma, surgery, internal bleeding, coexisting diseases, DNR, shock and less treatments (β blockers ASA etc.)

  • 3680 (4.7%) of the cohort received transfusions


Low hct and adverse outcome1
Low Hct and Adverse Outcome Infarction

  • Retrospective database reviews

  • These studies did not assess impact of transfusion or preoperative hematocrit

  • Lowest HCT groups were transfused at a significantly higher rate

  • Prospective, randomized trial results supporting these conclusions not available



Blood transfusion the global picture
Blood Transfusion: InfarctionThe Global Picture

  • >82,000,000 units donated per annum world wide

  • In the US, ~12,500,000 units of RBCs transfused

  • That’s one unit every 25 seconds!

WHO 2003


Risk and prevention of bloodborne diseases
Risk and InfarctionPrevention ofBloodborne Diseases

  • 43% of WHO participating countries (191) test their blood for

    • HIV

    • HCV

    • HBV

  • 13,000,000 units per annum are not tested!

  • 20% of the world’s population uses 80% of the safe blood supply

WHO 2003


Risks associated with blood transfusions
Risks InfarctionAssociated With Blood Transfusions

  • Clerical error

  • Transfusion reactions

  • Viral/bacterial infection

  • Immunomodulation

DHHS Jan, 2002


Shot serious hazards of transfusions
SHOT Infarction- Serious Hazards Of Transfusions

366 Reported

Disease

Purpura

"Complications"

TRALI

3%

6%

GVHD

8%

2%

Delayed

Blood Delivery

Reaction

Error

14%

52%

LM Williamson et al,

BMJ 1999;319:16-19

Acute Reaction

15%

  • ABO – clerical associated complications 1:16,0001

  • Krombach J et al, Human Error: The Persisting Risk of Blood Transfusion. Anesth Analg 2002;94:154-156


Transfusion safety in hospitals
Transfusion Safety in Hospitals Infarction

  • Linden JV et al. A report of104 transfusion errors in

  • NY State. Transfusion 1992;32:601-6 1:12,000

  • Robillard P et al. ABO incompatible transfusions,

  • acute and delayed hemolytic reaction in

  • Quebec. Transfusion 2002;42:25s 1:13,000

  • Baele PL et al. Bedside transfusion errors.

  • A prospective survey by the Belgium SAnGUIS group.

  • Vox Sang 1994;66:117-21 1:400


Decline in hiv hbv and hcv risks of transmission through transfusion

TRALI 1:5,000 Infarction

Bacteria 1:2,000

Clerical 1:12,000

Decline in HIV, HBV, and HCV Risks of Transmission Through Transfusion

HIV

HCV

1:100

1:1000

1:10,000

1:100,000

1:1,000,000

1:10,000,000

HBV

Risk of Infection per Unit Transfused

1983 1985 1987 1989 1991 1993 1995 1997 1999 2001

Year

Revised DonorDeferral Criteria

Non-A, Non-B Hepatitis

Surrogate Testing

p24 AntigenTesting

HCV and HIVNucleic AcidTesting

HCV AntibodyScreening

HIV AntibodyScreening

Adapted from Busch MP et al, JAMA 2003;289:959-62.

Aubuchon JP, Transfusion 2004;44:1377-1383.


Potential risks to the blood supply
Potential Risks to the Blood supply Infarction

  • Simian Foamy Virus (SFV)

  • West Nile virus

  • vCJD

  • Trypanosoma Cruzi


Trali
TRALI Infarction

  • 1:2000 transfused patients

  • FDA reports as the third most prevalent transfusion related mortality, after hemolysis and sepsis

  • Associated with: whole blood, RBC, platelets, FFP and cryo.

  • CHF – ARDS, fleeting or devastating

  • Two prominent theories

    • HLA class I and possible II, and monocyte antigens

    • 20% of women with multiple gestations carry class I antigens

    • Mixture of predisposition and infusion of blood related lipid derived mediators


Risks of allogeneic blood
Risks of Allogeneic Blood Infarction

‘TRIM’

Transfusion Related Immune

Modulation


Immune effects of blood
Immune Effects of Blood Infarction

  • Immunologic effects of autologous/allogenic blood Tx

    • 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-alfa

    • Increased suppressor T-cell activity

    • Reduced natural killer cell activity

McAlister FA et al, Br J Surg 1998;85:171-8.

Innerhofer P et al, Transfusion 1999;39:1089-96.


Immune modulation
Immune modulation Infarction

  • Allogeneic transfusion may enhance tumor recurrence following colorectal cancer resection (Heiss MM, J Clin Oncol 1994)

  • Allogeneic transfusion is associated with prolonged hospital LOS (Vamvakas EC, Transfusion 2000)

  • Allogeneic transfusion is associated with increased risk of bacterial infection (35%) and pneumonia (52%) (Carson JL, Transfusion 1999)

  • Length of storage of transfused RBCs was associated with postoperative pneumonia following CABG surgery, 5% per unit (Vamvakas EC, Transfusion 1999)


Donor leukocytes
Donor Leukocytes Infarction

  • Persistence of donor WBCs in trauma patients for up to 1.5 years after an allogeneic blood transfusion

  • ‘Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients’

  • 2 x 109 WBCs in one unit of packed red blood cells

  • 1 x 108 WBCs – centrifuged, buffy coat depleted

  • 1–5 x 106 WBCs – leukocyte filter, leukocyte-depleted

Lee TH et al, Blood 1999;93:3127–3139


Mortality rates are lower when leukocyte reduced blood is used
Mortality Rates Are Lower When Leukocyte Infarction-Reduced Blood Is Used

n=914

Bc=306

Ff=305

Sc=303

7.8%

Mortality Rate (%)

3.3%

Leukocyte reduction results in a significant reduction of mortality in patients undergoing cardiac surgery

van de Watering LMG et al, Circulation 1998;97:562–568


A prospective randomized clinical trial of universal wbc reduction

Men = 704 (49.4%) Infarction

Age = 69.4 (39.8, 84.3)

Surgical pts. (62%)

Non-surg. pts. 542 (38%)

Men = 675 (49.8%)

Age = 69.6 (42.0, 84)

Surgical pts. (60.5%)

Non-surg. pts. 535 (39.5%)

A prospective, randomized clinical trial of universal WBC reduction

Leukoreduced

Control

No demographic differences between groups

N=2780

Dzik WH et al, Transfusion 2002;42:1114-22.


Primary outcomes

In-hospital death Infarction 121 (8.5%)

LOS from the first transfusion avg. 10.6 days+ 14.5

Total hospital cost avg. $29,800+ $33.2K

median = $19,500)

Nonprophylactic antibiotic use after transfusion (days) 5.1

In-hospital death 122 (9.0%)

LOS from the first transfusion avg. 10.3 days+ 13.7

Total hospital cost avg.

$29,000+ $34K

(median = $19,200)

Nonprophylactic antibiotic use after transfusion (days) 4.5

Primary outcomes

Leukoreduced

Control

Dzik WH et al, Transfusion 2002;42:1114-22.


The impact of prbcs on nosocomial infection rates in icu
The Impact of PRBCs on InfarctionNosocomial Infection Rates in ICU

  • Retrospective database study of 1,717 patients using Project IMPACT

  • NI rates of 3 groups were compared:

    • Entire cohort

    • Transfusion group

    • Nontransfusion group

  • Patients stratified for age, gender, and probability of survival using Mortality Prediction Model (MPM-0) scores

Taylor RW et al, Crit Care Med 2002;30:1-6.


Nosocomial infection rates in critically ill patients
Nosocomial Infection Rates Infarctionin Critically Ill Patients

For each unit of PRBCs given, the odds of infection is increased by a factor of 1.5

P < .05

N = 1,717

n = 416

n = 1,301

Adjusted for severity of illness using MPM-0 scores, age, gender (Project IMPACT).

Taylor RW et al, Crit Care Med 2002;30:2249-54.


Mortality rates in critically ill patients
Mortality Rates in InfarctionCritically Ill Patients

P < .05

N = 1,717

n = 416

n = 1,301

Taylor RW et al, Crit Care Med 2002;30:2249-54.


Transfusion and outcome
Transfusion and Outcome Infarction

  • Retrospective, database study of long-term outcome in 1,915 patients after primary CABG

  • Excluded for death within 30 days of surgery

  • 546 patients transfused during hospitalization were matched by propensity score (age, gender, size, LOS, perfusion time and STS risk) with patients not transfused and 5-year mortality compared

  • 5-year mortality twice as high in transfused patients

  • After correction for comorbidity, 5-year mortality remained 70%higher in transfused group (p<0.001)

Engoren et al, Ann Thorac Surg 2002;74:1180-6


Univariate association rates of stroke and death in cabg with platelet transfusion
Univariate association rates of stroke and death in CABG with platelet transfusion

N=1720/248 from 6 RCT for Aprotinin FDA approval

Patients (%)

DEATH

STROKE

Spiess BD et al, Transfusion 2004;44:1143-1148


Summary
Summary with platelet transfusion

  • Risks

    • Infectious vs. non-infectious

  • Outcome data

    • Morbidity

      • Infection

      • MOF

    • Mortality –

  • Mechanism

    • WBC mediated

    • RBC mediated

    • Platelet/plasma

  • Storage lesion

  • Combination


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