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
Objectives
Risks of bleeding, subsequent hypovolemia, and acute anemia
– Compensatory mechanisms Macrocirculation Microcirculation
– Morbidity & mortality Risks of transfusions
Surgical BleedingVessel interruption
Surgical repairBleeding contained
No need for further action
Delay in repair Bleeding stops
Surgical repair Clotting
Factor consumption
Impaired clottingTransfusion of blood products
SIRSTransfusion relatedcomplications
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
MACMACROCIRCULATIONROCIRCULATION
MICMICROCIRCULATIONROCIRCULATION
PLASMAPLASMA
Baseline Delta max0
100
200Sy
stol
ic B
P (m
mHg
)
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
Baseline Delta max0
20
40
60
80He
art R
ate
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
Baseline Delta max0.0
0.5
1.0
1.5
2.0
2.5im
-a C
O2
gap
(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
Deliberate perioperative increase of DO2 >600 ml/min/m2 using volume loading and dopexamine in RCTProtocol (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
“Fluid” + Dobutamine / High Risk Surgery
01020304050607080
28 d Mortality pOP Complications
Control (n=18)Protocol (n=19)
%
Lobo et al, Crit Care Med 2000;28:3396-3404.
*
* p<0.05
*
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
Risks of Anemia
Anemia in CVD
Hgb = Mortality in CVDCarson/Gould – 300 Pts with Hgb <8
gm/dL - StratifiedCarson 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
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 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
366 Reported"Complications"
Blood Delivery Error52%
Acute Reaction15%
Delayed Reaction
14%
GVHD2%
TRALI8%
Purpura6%
Disease3%
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
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.
Ris
k of
Infe
ctio
n pe
r R
isk
of In
fect
ion
per
Uni
t Tra
nsfu
sed
Uni
t Tra
nsfu
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
2001 YearYearRevised DonorDeferral Criteria
Non-A, Non-B Hepatitis
Surrogate Testing
HIV AntibodyScreening
HCV AntibodyScreening
p24 AntigenTesting
HCV and HIVNucleic Acid
Testing
HIV HCV
HBV
Clerical 1:12,000Bacteria 1:2,000
TRALI 1:5,000
Potential Risks to the Blood supply
• Simian Foamy Virus (SFV)• West Nile virus• vCJD• Trypanosoma Cruzi
TRALI1:2000 transfused patientsFDA 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 devastatingTwo 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 BloodImmunologic 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 modulationAllogeneic 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 cells1 x 108 WBCs – centrifuged, buffy coat depleted1–5 x 106 WBCs – leukocyte filter, leukocyte-depleted
Lee TH et al, Blood 1999;93:3127–3139
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 Leukocyte Reduced
van de Watering LMG et al, Circulation 1998;97:562–568
Mor
talit
y Ra
te
(%)
7.8%
3.3%
n=914Bc=306Ff=305Sc=303
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.
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.
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.
5.9
15.4
2.9
02468
1012141618
Perc
ent o
f Pat
ient
s
All Patients
Transfused Patients
Non-transfusedPatients
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
13.6
24
10.2
0
5
10
15
20
25
Perc
ent o
f Pat
ient
s
All Patients
Transfused Patients
Non-transfusedPatients
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
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
02468
10
PrimaryCABG
ReopCABG
PrimaryCABG
ReopCABG
PlatesNo Plates
Pat
ient
s (%
)
STROKE DEATH
Spiess BD et al, Transfusion 2004;44:1143-1148
N=1720/248 from 6 RCT for Aprotinin FDA approval
SummaryRisks
Infectious vs. non-infectious
Outcome data Morbidity
– Infection– MOF
Mortality –Mechanism
WBC mediated RBC mediated Platelet/plasma
Storage lesionCombination
