Transcript title

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

Risks of bleeding, subsequent
hypovolemia, and acute
anemia
– Compensatory mechanisms
 Macrocirculation
 Microcirculation
– Morbidity & mortality

Risks of transfusions
Surgical Bleeding
Vessel interruption
Delay in repair
Surgical repair
Bleeding contained
No need for further action
Bleeding stops
Surgical repair
Clotting
Factor consumption
Transfusion of
blood products
Impaired clotting
Transfusion related
complications
SIRS
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
•Macrocirculation

Compensation

Shifting of blood flow
•Microcirculatory response

Cellular adaptation

Phenotype survival
SIR
MACROCIRCULATION
PLASMA
MICROCIRCULATION
Human Hemorrhage
and Blood Pressure
Systolic BP (mmHg)
200
25-30% bleed
(n=6)
100
0
Baseline
Delta max
Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81
Human Hemorrhage
and Heart Rate
80
25-30% bleed
(n=6)
Heart Rate
60
40
20
0
Baseline
Delta max
Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81
Human Hemorrhage
and Gastric Perfusion
p=0.002
im-a CO2 gap (kPa)
2.5
25-30% bleed
(n=6)
2.0
1.5
1.0
0.5
0.0
Baseline
Delta max
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)
(n=107)
Complications
Mortality
Dopexamine
0.68±0.16
5.7%
Control
1.35±0.02
22%
Boyd O. JAMA 1993;270:2699-2707.
P
0.008
0.015
“Fluid” + Dobutamine / High Risk
Surgery
80
70
60
%
50
40
*
30
20
10
Control (n=18)
Protocol (n=19)
*
0
28 d Mortality
* p<0.05
pOP Complications
Lobo et al, Crit Care Med 2000;28:3396-3404.
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 traumahemorrhage Schneider CP et al, Biochim Biophys Acta
2004;1689:22-32.
– Protective role
– Damaging role
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
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
 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 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
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
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 RBCs
transfused
That’s one unit every 25 seconds!
WHO 2003
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
Risks Associated With Blood
Transfusions
 Clerical
error
 Transfusion
reactions
 Viral/bacterial
infection
 Immunomodulation
DHHS Jan, 2002
SHOT - Serious Hazards Of Transfusions
TRALI
Purpura
Disease
6%
3%
GVHD 8%
366 Reported
"Complications"
2%
Delayed
Blood Delivery
Reaction
Error
14%
52%
Acute Reaction
15%
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
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
Risk of Infection per
Unit Transfused
Decline in HIV, HBV, and HCV Risks
of Transmission Through Transfusion
1:100
HIV
HCV
TRALI 1:5,000
HBV
1:1000
Bacteria 1:2,000
1:10,000
Clerical 1:12,000
1:100,000
1:1,000,000
1:10,000,000
1983 1985
Revised Donor
Deferral Criteria
1987
1989
Non-A, Non-B
Hepatitis
Surrogate Testing
HIV Antibody
Screening
Adapted from Busch MP et al, JAMA 2003;289:959-62.
Aubuchon JP, Transfusion 2004;44:1377-1383.
1991 1993
Year
HCV Antibody
Screening
1995
1997
p24 Antigen
Testing
1999 2001
HCV and HIV
Nucleic Acid
Testing
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 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
‘TRIM’
Transfusion Related Immune
Modulation
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.
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)
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
Mortality Rate (%)
Mortality Rates Are Lower When
Leukocyte-Reduced Blood Is Used
7.8%
10
8
n=914
Bc=306
Ff=305
Sc=303
6
3.3%
4
2
0
Allogeneic
Leukocyte Reduced
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
Leukoreduced
Control
Men = 675 (49.8%)
Men = 704 (49.4%)
Age = 69.4 (39.8, 84.3)
Surgical pts. (62%)
Non-surg. pts. 542 (38%)
Age = 69.6 (42.0, 84)
Surgical pts. (60.5%)
Non-surg. pts. 535 (39.5%)
No demographic differences between groups
N=2780
Dzik WH et al, Transfusion 2002;42:1114-22.
Primary outcomes
Control
 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
Leukoreduced
 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 = $19,500)
(median = $19,200)
 Nonprophylactic
 Nonprophylactic
antibiotic use after
antibiotic use after
transfusion (days) 5.1
transfusion (days) 4.5
Dzik WH et al, Transfusion 2002;42:1114-22.
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 2002;30:1-6.
Nosocomial Infection Rates
in Critically Ill Patients
18
Percent of Patients
16
14
For each unit of PRBCs
given, the odds of
infection is increased
by a factor of 1.5
All Patients
15.4
Transfused Patients
Non-transfused
Patients
12
10
8
6
5.9
P < .05
2.9
4
2
0
N = 1,717
n = 416
Adjusted for severity of illness using MPM-0 scores, age, gender (Project IMPACT).
Taylor RW et al, Crit Care Med 2002;30:2249-54.
n = 1,301
Mortality Rates in
Critically Ill Patients
24
25
Percent of Patients
P < .05
Transfused Patients
20
15
All Patients
Non-transfused
Patients
13.6
10.2
10
5
0
N = 1,717
Taylor RW et al, Crit Care Med 2002;30:2249-54.
n = 416
n = 1,301
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
Univariate association rates of
stroke and death in CABG with
platelet transfusion
N=1720/248 from 6 RCT for Aprotinin FDA approval
10
8
6
4
2
0
Plates
No Plates
Primary Reop Primary Reop
CABG CABG CABG CABG
STROKE
DEATH
Spiess BD et al, Transfusion 2004;44:1143-1148
Summary
Risks
Infectious vs. noninfectious
Outcome data
 Morbidity
– Infection
– MOF
 Mortality –
Mechanism
 WBC mediated
 RBC mediated
 Platelet/plasma
Storage lesion
Combination
