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BLOOD TRANSFUSION

Putu Agus Surya Panji


Department of Anesthesiology & Intensive Care
RS Sanglah Denpasar
Transfusion in the U.S.

• 12 million units given each year


• Common indications
– Bleeding
– Ischemia
– Resuscitation
– TRANQUILIZER…?
What can be still encountered in the
daily clinical practice
• Transfusion is performed merely
because the blood has been already
available
• Transfusion to reach Hb 10g/dL to
promote wound healing
• Whole blood is still ordered instead
of blood component
What can be still encountered in the
daily clinical practice
• Fresh blood sometimes ordered
• Transfusion to reach Hb 10g/dL
perioperatively as a minimal Hb
level for every pt
• FFP/albumin is given as a nutrient.
FFP is given without evidence of
blood coagulation disorder or as
plasma substitute
Transfusion in the ICU
• Retrospective review of patients in
ICU > 1 week
• 85% received pRBCs
• Average transfusion: 9.5 units
• Indications for transfusion
– No clear indication: 29%
– Low Hct: 19%

Corwin, et al. CHEST 1995; 108: 767.


Risks of Transfusion

• Infection
• Transfusion reaction
• Immunomodulatory
• Volume-related
Blood Borne Infections

Infection Estimated rate/ unit


transfused
HIV 1:420,000
Hepatitis B 1: 37,000
Hepatitis C 1: 62,000
Blood and the Immune System

• Despite filters, WBCs remain in pRBCs


• Transfusion promotes cytokine release
• Alters cellular immunity:
– Decreased: CD4 cells, NK cells,
IL-2 production
– Increases: B cells, CD8
suppressor cells, PGE2
Blood and the Immune System

• Design: Prospective, observational study


• Subjects: CABG patients
• Comparisons: transfused vs. no
transfusion intraoperatively
• Measurements: IL-6
• n=136

Fransen et al. CHEST 1999; 116: 1233.


Blood and the Immune System

900

675
IL-6 (ng/ml)

No Transfusion
450 Transfusion

225

0
Pre X-on 0 0.5 4 8 18
Reperfusion (hrs)
Do the immune effect of blood
have clinical implications?
Transfusion and Outcomes
Colorectal Cancer

• Design: Retrospective
• Subjects: Colorectal cancer resection
• Comparison: transfused vs. non-transfused
• Endpoints: hospital charges and LOS
• Controlled for multiple confounders
(comorbidity, age, gender, ICU admission,
etc)
• n=487
Vamvakas et al, Arch Pathol Lab Med 1998; 122: 145.
Transfusion and Outcome
Transfused Not p
Transfused
Post-op 34.2% 19.0% 0.0004
Infection
LOS (days) 16.7 10.3 0.0001
Charges ($) 28,101 15,978 0.0001

After controlling for confounders, each unit transfusion


increased charges by 2.0% (p <0.001)
Transfusion and Outcome
Nosocomial pneumonia after pRBC in CABG

• Design: Case-control
• Subjects: s/p CABG
• Endpoints: Nosocomial pneumonia
• n= 45 cases and 90 controls

Leal-Noval, et al. Crit Care Med 2000; 28: 935


Relationship between the
units of blood transfused and
the percentage of infections
Transfusion and Outcome

• Use of pRBCs alters immune system


• Immune dysregulation has significant
clinical correlates
• Multiple endpoints adversely affected by
use of pRBCs
• But why are we transfusing anyway?
Blood Bank Storage

• CPD Storage 2,3-DPG depletion


• O.D.C. left-shifted oxygen ( P50)
• Oxygen unloading impaired
DPG and O2 Carrying

12
Fresh Blood
ml )2/100 ml blood

9
1-Week-Old Blood Activated Blood
6

0
0 5 10 15 20 25
2,3 DPG (mmol/g Hb)

Hamasaki et al. Vox Sang 2000; 79:191-197.


Efek 2-3,DPG terhadap kurva disosiasi oksigen

P50 ↓ Inhibited Unloading


100 Alkalosis
90
↓ CO2
80 ↓ Temp
↓ 2-3,DPG
SaO2 %

70

60

50 P50↑ Better Unloading


40
Acidosis
30 P50 ↑ CO2
20
↑ Temp
10
↑ 2-3,DPG
0
0 20 40 60 80 100

PaO2 mmHg
Optimal Hemoglobin
• Hemoglobin crucial for oxygen delivery
• O2 Delivery [DO2]=
C.O. x Sa02 x Hgb x 1.34 x 10
• Originally thought that increasing delivery would
improve outcomes (Shoemaker 1988)
• Multiple studies evaluated
– Increasing CO with dobutamine
– Increasing O2 carrying capacity with
transfusion
Supraphysiologic

O2 Delivery

Author n Proportion Control Treatment p


achieving Group Group
goal (%) Mortality (%) Mortality (%)
Yu 1993 67 60 34 34 0.99

Hayes 100 44 34 54 0.04


1994
Gattinoni 762 67 48 52 0.64
1995
Transfusion and Oxygen
Delivery
• Subjects: 23 patients with septic shock
• Intervention: transfusion of 3u pRBCs
• Measurements: O2 uptake and gastric tonometry
• Results
– No increase in O2 uptake with
transfusion
– Inverse association between gastric pH
and age of blood (r=-0.71, p < 0.001)
– No beneficial impact of transfusion in
sepsis but at cost of splanchnic ischemia

Marik P, et al. JAMA 1993; 269: 3024.


Optimal Hemoglobin
• No evidence that increasing O2 delivery
changes mortality in general ICU population
• May actually be harmful
• ATS position statement:
– “We conclude that continued
aggressive attempts to increase
O2 delivery are unwarranted.”
Optimal Hemoglobin

• Clearly higher Hgb achieved via transfusion


is not helpful and may be harmful
• If SvO2 decreases, it means that oxygen
delivery is not high enough to meet tissue • Increases in SvO2 combined with rising
needs lactate levels indicate tissues are unable to
• This might be due to inadequate oxygen extract oxygen
delivery (poor saturation, anemia, insufficient •
cardiac output) This can be seen in such things as septic
shock, cyanide toxicity, carbon monoxide,
• Or, it might be due to increased tissue methemoglobin
extraction (fever, shivering, thyrotoxicosis, – Might also indicate hypothermia, shunt,
agitation, exercise, etc.) May indicate inotrope excess, etc.
improvement of previous poor situation
Guidelines for Transfusion in
Trauma
Guidelines for Transfusion in
Trauma
Early Goal-Directed Therapy In The
Treatment Of Severe Sepsis And
Septic Shock

E. Rivers et al. N Eng J Med. Nov 2001. 1368

• 263 patients. Admitted via Emergency


Room.
• Severe sepsis or sepsis syndrome.
• Random allocation 133 Standard therapy
130 patients Early goal-directed therapy
(EGDT) in ER before arrival in ICU.
RESULTS.

Rivers N Eng J M.2001.345:1368-1377

Standard Rx EGDT p

APACHE II 20.4 21.4 0.27

SAPS II 48.8 51.2 0.08

In hospital mortality 46.5% 30.5% 0.001

28 day mortality 49% 33.3% 0.01

60 day mortality 56.9% 44.3% 0.01


Marik, NEJM 2002, Goal-Directed Therapy for Severe
Sepsis, correspondence.

• There is good evidence that packed red cells do not


increase oxygen consumption (at least in the first 24
hours) in patients with sepsis (Marik, 1993).
Paradoxically, "old" units of packed red cells may cause
tissue dysoxia in patients with sepsis (Marik, 1993).
• Furthermore, transfusions of packed red cells may
increase mortality in critically ill patients with sepsis
(Hebert 1999, Purdy 1997)
• We wholeheartedly endorse the concept of early,
aggressive volume resuscitation in patients with
sepsis, but please do not transfuse blood and do not
be misled by the SmvO2 or ScvO2
Is there a lower threshold?
Transfusion Requirements in
Critical Care

• Multicenter, RCT
• Subjects
– Acutely ill in ICU, Hgb < 9.0
– Excluded if: chronic anemia, ongoing
bleeding, admission after CABG

Hebert et al. NEJM 1999; 340:409-17


Transfusion Requirements in
Critical Care

• Randomized to 2 strategies
– Liberal strategy:
• Maintain Hgb between 10-12
– Restrictive strategy:
• Maintain Hgb between 7-9
• Endpoints
– All cause mortality, MSOF
– Predefined subgroups: age >
55, CAD, APACHE II > 20
Transfusion Requirements in
Critical Care
Restrictive Liberal p
(n=418) (n=420)
ICU mortality 13.4% 16.2% 0.29

Death (30d) 18.7% 23.3% 0.11

ICU LOS 11.0 11.5 0.53

MODS 8.3 8.8 0.10

MI 0.7% 2.9% 0.02


Transfusion Requirements in Critical
Care
Patients with APACHE II < 20
100

90
Survival (%)

80 Restrictive
p=0.02 Liberal
70

60

50
0 5 10 15 20 25 30
Days
Transfusion Requirements in Critical
Care

Patients Younger than 55


100
90
Survival (%)

80 Restrictive
p=0.02 Liberal
70
60
50
0 5 10 15 20 25 30
Days
Transfusion Requirements in
Critical Care
• Conclusions
– Lower transfusion threshold was as
effective as higher trigger
– Lower threshold superior in some
subgroups
– Mechanism of worse outcomes with
liberal strategy unclear (? promotes
cytokine cascade, increased risk of
ARDS)
Transfusion Requirements in
Critical Care
• Editorial comment in NEJM
“This study has made it clear that a
single threshold for transfusion in all
patients is not appropriate…… With this
knowledge, more physicians will be able
to follow the dictum “first do no harm,”
and we will have a surplus of blood
rather than a shortage.”
Ely et al. NEJM 1999: 340: 468.
Do not tranfuse for following
reasons !:
• to improve general sense of well
being
• as hematinic agent
• to expand vascular volume
• as prophylaxis if there is no risk
factor
Decision to transfuse RBC: Hb
is important
but not the sole deciding factor
• Sign & symptoms of hypoxia,
ongoing blood loss, the risk of
anemia & the risk of transfusion
• Cardio pulmonary reserve
• Volume of blood loss
• O2 consumption
• Atherosclerotic disease
Matur Suksma