Transcript Slide 1

Red Cell Transfusion in Critical Care
Patients
Alan Tinmouth, MD MSc
University of Ottawa Centre for Transfusion Research,
Ottawa Health Research Institute and the Ottawa Hospital
November 2009
Objectives
• Review the seminal observational and
randomized clinical trials evaluating red cell
transfusions in the critically ill.
• Understand the limitations of the current
evidence surrounding red cell transfusions.
• Understand the limits and benefits of alternatives
/ strategies to reduce the need for red cell
transfusions.
Case 1
Hebert, Crit Care Med 2005; 33; 7.
Anemia in the critically ill is very
common
• 95% anemic by 3rd day
in ICU
• 40 – 45% of patients will
receive RBCs
• Average = 5 units RBC
Vincent et al, JAMA 2002; Corwin et al, CCM 2004
RBC Transfusions in Critical Care and
Cardiac Surgery in Canada, 1998-2000
Hutton et al. CJA 2005
Purpose of an RBC transfusion
Increase hemoglobin
levels.
Increase O2 delivery
and consumption.
Decrease morbidity
and mortality.
The Role of Hemoglobin in O2 Delivery
(1) DO2 = CO x (%sat x 1.39 x Hb)
(2) CO = HR x stroke volume
DO2
CO
%Sat
Hb
1.39
= O2 Delivery (ml/L)
= Cardiac output(L/min)
= % saturation of Hb
= Hemoglobin (g/L)
= O2 carried in blood (ml/L)
Oxygen Delivery and RBC Transfusion
Delivery Dependent
Delivery Independent
VO2
Critical DO2
DO2
• At least 19 clinical studies evaluating impact RBCs
on oxygen kinetics in humans
• Uniform increase in DO2 but not VO2
Hebert et al, CMAJ, 1997
Oxygen Delivery and Consumption
following RBC transfusion
Suttner et al. Anesth Analg 2004; 99: 2-11
Transfusion Requirements in
Critical Care (TRICC)
Hebert PC, et al. A multicenter, randomized, controlled
clinical trial of transfusion requirements in critical
care. N Engl J Med. 1999;340(6):409-17
Purpose:
To determine if a restrictive and liberal
red cell transfusion strategy are
equivalent in terms of effects on
mortality and morbidity in volume
resuscitated critically ill patients
Hebert et al. NEJM 321: 151-156, 1999
TRICC Study
Study design: Multicentre RCT
Setting: 25 ICUs across Canada
Study Population: Included Hb< 9.0 g/dl within
72 hrs and excluded patients with active
blood loss (3.0 g/dl decrease or >3 unit
transfusion in 12 hrs)
Intervention: 7.0 g/dl vs 10.0 g/dl hemoglobin
trigger
Outcomes: 30 day all-cause mortality and organ
failure
Hebert et al. NEJM 321: 151-156, 1999
Hemoglobin (g/L)
Hemoglobins over time
Liberal strategy
120
110
100
90
80
70
60
50
40
30
20
10
0
Restrictive strategy
p<0.01
0
5
10
15
Time (Days)
Hebert et al. NEJM 321: 151-156, 1999
20
25
30
Survival of all patients over 30 days
100
Restrictive strategy
Survival (%)
90
18.7%
80
Liberal strategy
23.3%
70
p=0.10
60
50
0
5
10
15
Time (Days)
Hebert et al. NEJM 321: 151-156, 1999
20
25
30
Survival of patients < 55 years of age
Hebert et al. NEJM 321: 151-156, 1999
TRICC – Mortality and MODS
Outcomes
Liberal
(n=420)
Restrictive
(n=418)
P-Value
Mortality No.(%)
30-day
60-day
ICU
Hospital
98 (23.3)
111(26.5)
68 (16)
118(28.1)
78 (18.7)
95(22.8)
56 (13)
93(22.3)
0.11
0.23
0.29
0.05
Organ Dysfunction
MODS
MODS*
Change in MODS
8.8 ± 4.4
11.8 ± 7.7
1.26 ± 4.30
8.3 ± 4.6
10.7 ± 7.5
0.79 ± 4.26
0.10
0.03
0.15
Hebert et al. NEJM 321: 151-156, 1999
Case 1
Hebert, Crit Care Med 2005; 33; 7.
ICU Responses 1997 and 2003
Hebert, Crit Care Med 2005; 33; 7.
RBC transfusions and risk of death
Marik and Corwin, CCM 2008;36:2667
Can we trust these studies?
Inferences from these studies are weakened
because:
• Logic of transfusions always being harmful??
• Retrospective with limited data
• Minimal adjustment for confounding factors
• Timing of RBCs unknown
• Trigger unknown…admission hematocrit/nadir
hematocrit
• Main culprit: “Confounding by Indication”
– higher acuity → more aggressive care
Adverse Effects Associated with Transfusion
Other adverse
effects of
leukocytes
Fever
Neutrophilia
Flushing
Proinflammatory
Capillary leak
TRALI / ARDS
MOF
PLASMA
Cleavage / activation of
Plasma proteins
Kinins
Complement
Histimine
Cytokines
Microaggregates
BUFFY COAT
Thrombosis
? ARDS
RES Blockade
Microvascular Pathology
Procoagulants
Thrombosis
RED CELLS
Haemolysis
Impaired O2 delivery
Acidosis
K+, Na+, NH4+
Hypothermia
Glucose
Plasticisers
Hypotension
Flushing
Anxiety
GIT Symptoms
Pain
Proinflammatory
Chemical,
Metabolic
&
Physical
Billirubin
LDH
Iron
Jaundice
1. Impaired RBC survival
2. Reduced efficacy
3. Adverse effects
Consequences of Biochemical and
BioMechanical Changes in Stored RBCs
• Left shift of oxygenhemoglobin dissociation
curve
• Loss of red blood cell
deformability
• Increased RBC aggregation
• Increased RBC adhesion to
endothelial cells
• Release of hypercoagulable
microvessicles
• Increased NO scavenging
• Accumulation of cytokines
Tinmouth. Transfusion 2006
Case 3
Hebert, Crit Care Med 2005; 33; 7.
TRICC and acuity of illness
APACHE II =< 20
APACHE II > 20
Restrictive strategy
100
100
90
80
Survival (%)
Survival (%)
90
Liberal strategy
70
p = 0.02
60
50
0
5
10
15
20
25
30
Time (Days)
Hebert et al. NEJM 321: 151-156, 1999
Restrictive strategy
80
70
Liberal Strategy
60
50
p=0.54
0
5
10
15
20
Time (Days)
25
30
Goal Directed Therapy in Early Sepsis
Rivers et al. NEJM 2004; 345: 1368
Goal Directed Therapy in Early Sepsis
Rivers et al. NEJM 2004; 345: 1368
Case 3
ICU Responses 1997 and 2003
Hebert, Crit Care Med 2005; 33; 7.
Case 2
Hebert, Crit Care Med 2005; 33; 7.
TRICC – Cardiovascular Disease
Patients with Ischemic Heart
Disease (n=257)
Patients with cardiovascular
diseases (n=357)
100
L ib e ra l
90
R e stric tiv e
80
70
p = 0.95
60
50
0
5
10
15
20
25
30
Tim e (Days)
Hebert et al. NEJM 321: 151-156, 1999
Su rv iv a l (% )
Su rv i v a l (% )
100
L ib e ra l
90
R e stric tiv e
80
70
p = 0. 30
60
50
0
5
10
15
20
Tim e (Da y s )
25
30
Complications during the ICU Stay
Complication
Liberal
(n=420)
Restrictive
(n=418)
P Values
Cardiac No. (%)
Myocardial Infarction
Pulmonary Edema
Angina
Cardiac Arrest
Pulmonary No. (%)
ARDS
Pneumonia
88 (21.0)
12 (2.9)
45 (10.7)
9 (2.1)
33 (7.9)
122 (29.1)
48 (11.4)
86 (20.5)
55 (13.2)
3 (0.7)
22 (5.3)
5 (1.2)
29 (6.9)
106 (25.4)
32 (7.7)
87 (20.8)
<0.01
0.02
<0.01
0.28
0.6
0.22
0.06
0.92
Hebert et al. NEJM 321: 151-156, 1999
RBC transfusions in acute MI
Wu. NEJM 2001; 345: 1230.
RBC transfusion in ACS
• Transfused patients were older, had more comorbidities and higher mortality rates
Rao. NEJM 2001; 345: 1230.
RBC transfusion in ACS
• Adjusted analysis showed higher mortality rate
associated with transfusions
– No associated with harm for nadir hct of 0.20-0,25
– Increased mortality for nadir hct > 0.30
Rao. NEJM 2001; 345: 1230.
Case 2
Hebert, Crit Care Med 2005; 33; 7.
ICU Responses 1997 and 2003
Hebert, Crit Care Med 2005; 33; 7.
Case 4
Walsh, Transf 2009; epub.
TRICC and mechanical ventilation
Hebert et al. NEJM 321: 151-156, 1999
Case 4
Walsh, Transf 2009; epub.
Case 5
• 28 year old Jehova Witness. Peripartum
hemorrage taken to OR and hysterectomy
performed. Bleeding now controlled.
Admitted to ICU post-op with Hgb 28 g/L.
Treatment recommendations ?
Alternatives to Red Cell Transfusions
• Erythropoietin
• Iron replacement
• Folate
Other
– Factor VIIa for bleeding
– Reduce phlebotomy – pediatric tubes
EPO in Critical Care – Part 1
Corwin, JAMA 2002; 288: 2827.
EPO in Critical Care – Part 1
• EPO raised hemoglobin (13.2 g/L vs. 9.4 g/L)
• EPO resulted in 19% reduction in number of
units RBCs transfused
EPO in Critical Care – part II
• EPO raised increased hemoglobin (16 g/L vs. 12 g/L, p <
0.001) and resulted in higher hemoglobin levels.
• No difference in transfusion rates with restrictive
transfusion policy
Corwin, NEJM 2007; 357: 965.
EPO in Critical Care – part II
Thrombosis
Mortality
Corwin, NEJM 2007; 357: 965.
Conclusions
• In critical care patients, restrictive RBC
transfusion strategy is not worse than liberal
transfusion strategy
– Patients not likely to benefit from RBC transfusion are
only likely to be harmed
• Results of TRICC not generalizable to all
critically ill patients
– e.g. cardiac and bleeding patient
• Alternatives to transfusions also have adverse
effects
– “best transfusion is not simply transfusion not given”