Surgical%20Bleeding%20and%20Transfusions:%20The%20Issues%20in%202004

1
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

2
Objectives

• Risks of bleeding, subsequent hypovolemia, and
  acute anemia
• Compensatory mechanisms
• Macrocirculation
• Microcirculation
• Morbidity mortality
• Risks of transfusions

3
Surgical Bleeding
4
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
5
Bleeding and Hemorrhage

• Macrocirculation
• Compensation
• Shifting of blood flow
• Microcirculatory response
• Cellular adaptation
• Phenotype survival

SIR
6
MACROCIRCULATION
PLASMA
MICROCIRCULATION
7
Human Hemorrhage and Blood Pressure
25-30 bleed (n6)
Hamilton-Davies C et al, Intensive Care Med
199723276-81
8
Human Hemorrhage and Heart Rate
25-30 bleed (n6)
Hamilton-Davies C et al, Intensive Care Med
199723276-81
9
Human Hemorrhage and Gastric Perfusion
p0.002
25-30 bleed (n6)
Hamilton-Davies C et al, Intensive Care Med
199723276-81
10
Fluid Dobutamine / High Risk Surgery

• Deliberate perioperative increase of DO2 gt600
  ml/min/m2 using volume loading and dopexamine in
  RCT
• Protocol (dopexamine) group had higher DO2 preop
  and postop (plt0.001)

Boyd O. JAMA 19932702699-2707.
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Fluid Dobutamine / High Risk Surgery



plt0.05
Lobo et al, Crit Care Med 2000283396-3404.
12
Surgery, trauma and the inflammatory response

• Surgical trauma hyperinflammation versus
  immunosuppression? Menger MD, Vollmar
  B.Langenbecks Arch Surg 2004389475-84.
• 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 2004168922-32.
• Protective role
• Damaging role

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Risks of Anemia
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Anemia in CVD

• Hgb ? Mortality in CVD
• Carson/Gould 300 Pts with Hgb lt8 gm/dL -
  Stratified
• Carson JL et al, Lancet 19963481055-60
• Hgb lt 9.5 g/dL high risk with CVD
• Hebert PC at al, Am J Respir Crit Care Med
  19971551618-23
• Hgb lt 7.0 g/dL acceptable with normal coronary
  circulation

15
Low Hct and Adverse Outcome

• Lowest CPB HCT of lt14 in low risk patients and
  lt17 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 lt22 (Habib RH, J Thorac Cardiovasc Surg 2003)

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Blood transfusion in Elderly Patients with Acute
Myocardial InfarctionWu WC et al, NEJM
20013451230-36

• 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 (ß blockers ASA etc.)
• 3680 (4.7) of the cohort received transfusions

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Low Hct and Adverse Outcome

• 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

19
Risks of Blood Transfusions
20
Blood TransfusionThe Global Picture

• gt82,000,000 units donated per annum world wide
• In the US, 12,500,000 units of RBCs transfused
• Thats one unit every 25 seconds!

WHO 2003
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Risk and Prevention of Bloodborne 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 worlds population uses 80 of the
  safe blood supply

WHO 2003
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Risks Associated With Blood Transfusions

• Clerical error
• Transfusion reactions
• Viral/bacterial infection
• Immunomodulation

DHHS Jan, 2002
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SHOT - 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 199931916-19
Acute Reaction
15

• ABO clerical associated complications
  116,0001
• Krombach J et al, Human Error The Persisting
  Risk of Blood Transfusion. Anesth Analg
  200294154-156

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Transfusion Safety in Hospitals

• Linden JV et al. A report of104 transfusion
  errors in
• NY State. Transfusion 199232601-6 112,000
• Robillard P et al. ABO incompatible
  transfusions,
• acute and delayed hemolytic reaction in
• Quebec. Transfusion 20024225s 113,000
• Baele PL et al. Bedside transfusion errors.
• A prospective survey by the Belgium SAnGUIS
  group.
• Vox Sang 199466117-21 1400

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Decline in HIV, HBV, and HCV Risks of
Transmission Through Transfusion
HIV
HCV
1100 11000 110,000 1100,000 11,000,000 110,0
00,000
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
2003289959-62. Aubuchon JP, Transfusion
2004441377-1383.
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Potential Risks to the Blood supply

• Simian Foamy Virus (SFV)
• West Nile virus
• vCJD
• Trypanosoma Cruzi

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TRALI

• 12000 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

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Risks of Allogeneic Blood
TRIM Transfusion Related Immune Modulation
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Immune Effects of Blood

• 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 199885171-8. Inner
hofer P et al, Transfusion 1999391089-96.
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Immune modulation

• 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)

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Donor Leukocytes

• 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
• 15 x 106 WBCs leukocyte filter,
  leukocyte-depleted

Lee TH et al, Blood 19999331273139
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Mortality Rates Are Lower When Leukocyte-Reduced
Blood Is Used
n914 Bc306 Ff305 Sc303
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
199897562568
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A prospective, randomized clinical trial of
universal WBC reduction
Leukoreduced
Control

• Men 675 (49.8)
• Age 69.6 (42.0, 84)
• Surgical pts. (60.5)
• Non-surg. pts. 535 (39.5)

• Men 704 (49.4)
• Age 69.4 (39.8, 84.3)
• Surgical pts. (62)
• Non-surg. pts. 542 (38)

No demographic differences between groups N2780
Dzik WH et al, Transfusion 2002421114-22.
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Primary outcomes
Leukoreduced
Control

• 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

• In-hospital death 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

Dzik WH et al, Transfusion 2002421114-22.
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The Impact of PRBCs on Nosocomial 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 2002301-6.
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Nosocomial Infection Rates in Critically Ill
Patients
For each unit of PRBCs given, the odds of
infection is increased by a factor of 1.5
P lt .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 2002302249-54.
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Mortality Rates in Critically Ill Patients
P lt .05
N 1,717
n 416
n 1,301
Taylor RW et al, Crit Care Med 2002302249-54.
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Transfusion and Outcome

• 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 70higher in transfused group
  (plt0.001)

Engoren et al, Ann Thorac Surg 2002741180-6
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Univariate association rates of stroke and death
in CABG with platelet transfusion
N1720/248 from 6 RCT for Aprotinin FDA approval
Patients ()
DEATH
STROKE
Spiess BD et al, Transfusion 2004441143-1148
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Summary

• Risks
• Infectious vs. non-infectious
• Outcome data
• Morbidity
• Infection
• MOF
• Mortality
• Mechanism
• WBC mediated
• RBC mediated
• Platelet/plasma
• Storage lesion
• Combination