Aryeh Shander, MD,
FCCM, FCCP
Surgical Bleeding and
Transfusions: The
Issues in 2004
Chief, Dept of Anesthesiology, Critic...
Objectives
Risks of bleeding, subsequent
hypovolemia, and acute
anemia
– Compensatory mechanisms
• Macrocirculation
• Micr...
Surgical Bleeding
Vessel interruption
Surgical repair
Bleeding contained
No need for further action
Delay in repair
Bleedi...
Consequences of untreated
Hypovolemia
American College of Surgeons (ACS)
Advance Trauma Life Support (ATLS)
Society of Cri...
Bleeding and Hemorrhage
•Macrocirculation
Compensation
Shifting of blood flow
•Microcirculatory response
Cellular adaptati...
MACMACROCIRCULATIONROCIRCULATION
MICMICROCIRCULATIONROCIRCULATION
PLASMAPLASMA
Base line De lta max
0
100
200SystolicBP(mmHg)
Human Hemorrhage
and Blood Pressure
25-30% bleed25-30% bleed
(n=6)(n=6)
Ham...
Base line De lta max
0
20
40
60
80
HeartRate
Human Hemorrhage
and Heart Rate
25-30% bleed25-30% bleed
(n=6)(n=6)
Hamilton-...
Base line De lta max
0.0
0.5
1.0
1.5
2.0
2.5
im-aCO2gap(kPa)
25-30% bleed25-30% bleed
(n=6)(n=6)
p=0.002p=0.002
Human Hemo...
Deliberate perioperative increase of DO2 >600
ml/min/m2
using volume loading and
dopexamine in RCT
Protocol (dopexamine) g...
“Fluid” + Dobutamine / High Risk
Surgery
0
10
20
30
40
50
60
70
80
28 d Mortality pOP Complications
Control (n=18)
Protoco...
Surgery, trauma and the
inflammatory response
Surgical trauma: hyperinflammation versus
immunosuppression? Menger MD, Voll...
Risks of Anemia
Anemia in CVD
↓ Hgb = ↑ Mortality in CVD
Carson/Gould – 300 Pts with Hgb <8
gm/dL - Stratified
Carson JL et al, Lancet
199...
Low Hct and Adverse Outcome
Lowest CPB HCT of <14% in low risk patients and
<17% in high risk patients associated with do...
Blood transfusion in Elderly Patients with
Acute Myocardial Infarction
Wu WC et al, NEJM 2001;345:1230-36
Cooperative Card...
Low Hct and Adverse Outcome
 Retrospective database reviews
 These studies did not assess impact of
transfusion or preop...
Risks of Blood
Transfusions
Blood Transfusion:
The Global Picture
>82,000,000 units donated per
annum world wide
In the US, ~12,500,000 units of RBC...
Risk and Prevention of Bloodborne
Diseases
43% of WHO participating countries (191)
test their blood for
HIV
HCV
HBV
13,00...
Risks Associated With Blood
Transfusions
Clerical error
Transfusion reactions
Viral/bacterial infection
Immunomodulation
D...
SHOT - Serious Hazards Of Transfusions
366 Reported
"Complications"
Blood Delivery
Error
52%
Acute Reaction
15%
Delayed
Re...
Transfusion Safety in Hospitals
• Linden JV et al. A report of104 transfusion errors in
NY State. Transfusion 1992;32:601-...
Decline in HIV, HBV, and HCV Risks
of Transmission Through Transfusion
Adapted from Busch MP et al, JAMA 2003;289:959-62.
...
Potential Risks to the Blood supply
• Simian Foamy Virus (SFV)
• West Nile virus
• vCJD
• Trypanosoma Cruzi
TRALI
1:2000 transfused patients
FDA reports as the third most prevalent transfusion
related mortality, after hemolysis an...
Risks of Allogeneic Blood
‘TRIM’
Transfusion Related Immune
Modulation
Immune Effects of Blood
Immunologic effects of
autologous/allogenic blood Tx
Decreased T-cell proliferation
Decreased CD3,...
Immune modulation
Allogeneic transfusion may enhance tumor recurrence
following colorectal cancer resection (Heiss MM, J C...
Donor Leukocytes
Persistence of donor WBCs in trauma patients for up to 1.5 years after
an allogeneic blood transfusion
‘S...
Leukocyte reduction results in a significant reduction of mortality in
patients undergoing cardiac surgery
Mortality Rates...
A prospective, randomized clinical
trial of universal WBC reduction
Men = 704 (49.4%)
Age = 69.4 (39.8, 84.3)
Surgical pts...
Primary outcomes
 In-hospital death 121
(8.5%)
 LOS from the first
transfusion avg. 10.6
days + 14.5
 Total hospital co...
The Impact of PRBCs on
Nosocomial Infection Rates in ICU
Retrospective database study of 1,717 patients
using Project IMPA...
5.9
15.4
2.9
0
2
4
6
8
10
12
14
16
18
PercentofPatients
All Patients
Transfused Patients
Non-transfused
Patients
N = 1,717...
13.6
24
10.2
0
5
10
15
20
25
PercentofPatients
All Patients
Transfused Patients
Non-transfused
Patients
N = 1,717 n = 416 ...
Transfusion and Outcome
• Retrospective, database study of long-term
outcome in 1,915 patients after primary CABG
• Exclud...
Univariate association rates of
stroke and death in CABG with
platelet transfusion
0
2
4
6
8
10
Primary
CABG
Reop
CABG
Pri...
Summary
Risks
Infectious vs. non-
infectious
Outcome data
Morbidity
– Infection
– MOF
Mortality –
Mechanism
WBC mediated
R...
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    1. 1. Aryeh Shander, MD, FCCM, FCCP Surgical Bleeding and Transfusions: The Issues in 2004 Chief, Dept of Anesthesiology, Critical Care and Hyperbaric Medicine Englewood Hospital & Medical Center and Associate Clinical Professor, Mount Sinai School of Medicine
    2. 2. Objectives Risks of bleeding, subsequent hypovolemia, and acute anemia – Compensatory mechanisms • Macrocirculation • Microcirculation – Morbidity & mortality Risks of transfusions
    3. 3. Surgical Bleeding Vessel interruption Surgical repair Bleeding contained No need for further action Delay in repair Bleeding stops Surgical repair Clotting Factor consumption Impaired clottingTransfusion of blood products SIRS Transfusion related complications
    4. 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. 5. Bleeding and Hemorrhage •Macrocirculation Compensation Shifting of blood flow •Microcirculatory response Cellular adaptation Phenotype survival SIR
    6. 6. MACMACROCIRCULATIONROCIRCULATION MICMICROCIRCULATIONROCIRCULATION PLASMAPLASMA
    7. 7. Base line De lta max 0 100 200SystolicBP(mmHg) Human Hemorrhage and Blood Pressure 25-30% bleed25-30% bleed (n=6)(n=6) Hamilton-Davies C et al,Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81Intensive Care Med 1997;23:276-81
    8. 8. Base line De lta max 0 20 40 60 80 HeartRate Human Hemorrhage and Heart Rate 25-30% bleed25-30% bleed (n=6)(n=6) Hamilton-Davies C et al,Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81Intensive Care Med 1997;23:276-81
    9. 9. Base line De lta max 0.0 0.5 1.0 1.5 2.0 2.5 im-aCO2gap(kPa) 25-30% bleed25-30% bleed (n=6)(n=6) p=0.002p=0.002 Human Hemorrhage and Gastric Perfusion Hamilton-Davies C et al,Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81Intensive Care Med 1997;23:276-81
    10. 10. 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. (n=107) Dopexamine Control P Complications 0.68±0.16 1.35±0.02 0.008 Mortality 5.7% 22% 0.015 “Fluid” + Dobutamine / High Risk Surgery
    11. 11. “Fluid” + Dobutamine / High Risk Surgery 0 10 20 30 40 50 60 70 80 28 d Mortality pOP Complications Control (n=18) Protocol (n=19) % Lobo et al, Crit Care Med 2000;28:3396-3404. * * p<0.05 *
    12. 12. 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
    13. 13. Risks of Anemia
    14. 14. 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
    15. 15. 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)
    16. 16. Blood transfusion in Elderly Patients with Acute Myocardial Infarction Wu 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
    17. 17. 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
    18. 18. Risks of Blood Transfusions
    19. 19. Blood Transfusion: The 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
    20. 20. 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 world’s population uses 80% of the safe blood supply WHO 2003
    21. 21. Risks Associated With Blood Transfusions Clerical error Transfusion reactions Viral/bacterial infection Immunomodulation DHHS Jan, 2002
    22. 22. SHOT - Serious Hazards Of Transfusions 366 Reported "Complications" Blood Delivery Error 52% Acute Reaction 15% Delayed Reaction 14% GVHD 2% TRALI 8% Purpura 6% Disease 3% LM Williamson et al, BMJ 1999;319:16-19 • 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
    23. 23. Transfusion Safety in Hospitals • 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
    24. 24. Decline in HIV, HBV, and HCV Risks of Transmission Through Transfusion Adapted from Busch MP et al, JAMA 2003;289:959-62. Aubuchon JP, Transfusion 2004;44:1377-1383. RiskofInfectionperRiskofInfectionper UnitTransfusedUnitTransfused 1:100 1:1000 1:10,000 1:100,000 1:1,000,000 1:10,000,000 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 YearYearRevised Donor Deferral Criteria Non-A, Non-B Hepatitis Surrogate Testing HIV Antibody Screening HCV Antibody Screening p24 Antigen Testing HCV and HIV Nucleic Acid Testing HIV HCV HBV Clerical 1:12,000 Bacteria 1:2,000 TRALI 1:5,000
    25. 25. Potential Risks to the Blood supply • Simian Foamy Virus (SFV) • West Nile virus • vCJD • Trypanosoma Cruzi
    26. 26. TRALI 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
    27. 27. Risks of Allogeneic Blood ‘TRIM’ Transfusion Related Immune Modulation
    28. 28. 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 1998;85:171-8. Innerhofer P et al, Transfusion 1999;39:1089-96.
    29. 29. 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)
    30. 30. 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 1–5 x 106 WBCs – leukocyte filter, leukocyte-depleted Lee TH et al, Blood 1999;93:3127–3139
    31. 31. Leukocyte reduction results in a significant reduction of mortality in patients undergoing cardiac surgery Mortality Rates Are Lower When Leukocyte-Reduced Blood Is Used 0 2 4 6 8 10 Allogeneic Leuk ocyt e Reduced van de Watering LMG et al, Circulation 1998;97:562–568 MortalityRate(%) 7.8% 3.3% n=914 Bc=306 Ff=305 Sc=303
    32. 32. A prospective, randomized clinical trial of universal WBC reduction Men = 704 (49.4%) 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%) Control Leukoreduced No demographic differences between groups N=2780 Dzik WH et al, Transfusion 2002;42:1114-22.
    33. 33. Primary outcomes  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  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 Control Leukoreduced Dzik WH et al, Transfusion 2002;42:1114-22.
    34. 34. 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) scoresTaylor RW et al, Crit Care Med 2002;30:1-6.
    35. 35. 5.9 15.4 2.9 0 2 4 6 8 10 12 14 16 18 PercentofPatients All Patients Transfused Patients Non-transfused Patients N = 1,717 n = 416 n = 1,301 P < .05 Nosocomial Infection Rates in Critically Ill Patients Adjusted for severity of illness using MPM-0 scores, age, gender (Project IMPACT). Taylor RW et al, Crit Care Med 2002;30:2249-54. For each unit of PRBCs given, the odds of infection is increased by a factor of 1.5
    36. 36. 13.6 24 10.2 0 5 10 15 20 25 PercentofPatients All Patients Transfused Patients Non-transfused Patients N = 1,717 n = 416 n = 1,301 P < .05 Taylor RW et al, Crit Care Med 2002;30:2249-54. Mortality Rates in Critically Ill Patients
    37. 37. 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 70%higher in transfused group (p<0.001) Engoren et al, Ann Thorac Surg 2002;74:1180-6
    38. 38. Univariate association rates of stroke and death in CABG with platelet transfusion 0 2 4 6 8 10 Primary CABG Reop CABG Primary CABG Reop CABG Plates No Plates Patients(%) STROKE DEATH Spiess BD et al, Transfusion 2004;44:1143-1148 N=1720/248 from 6 RCT for Aprotinin FDA approval
    39. 39. Summary 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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