ré-évaluation du seuil transfusionnel philippe van der linden md, phd chu brugmann-huderf,...
TRANSCRIPT
Ré-évaluation du seuil transfusionnelRé-évaluation du seuil transfusionnel
Philippe Van der Linden MD, PhDCHU Brugmann-HUDERF, Université Libre de Bruxelles
Blood Transfusion Practice in Patients Undergoing Cesarean Section
Clinical scenario30-year-old womanCesarean section accompanied by profuse bleedingHemodynamically stable after crystalloid resuscitationEvidence of a slow ongoing blood loss
QuestionsAt what hemoglobin concentration would you transfuse the patient ?
At this threshold, how many units of RBCs would you transfuse?Would you measure Hb concentration before transfusing?
From Matot I et al. Am J Obstet Gynecol 190:462-7, 2004.P VdL
Blood Transfusion Practice in Patients Undergoing Cesarean Section
From Matot I et al. Am J Obstet Gynecol 190:462-7, 2004.
Gynecologists Anesthesiologists6 6,5 7 7,5 8 8,5 9 9,5 10
0
10
20
30
40
50
Transfusion threshold (g/dl)
% Responders
1 2 3 40
20
40
60
80
100
PRBCs units to be transfused
% Responders
p<0.01 p<0.05
P VdL
Anemia & Blood Transfusion in Critical Care
From Vincent JL et al. JAMA 288:1499-1507, 2002.
E.U. prospective study (1999)146 units; 3534 patients
Hb < 10 g/dl at admission: 29%
0
2
4
6
8
10
12
14
Hemoglobin (g/dl)
Pretransfusion Hb
0
10
20
30
40
50
Patients (%)
ICU transfusion rate
37
Higher transfusion rate:older patients, longer ICU stay
RBC transfusion associated with:decreased organ function, mortality
P VdL
Anemia & Blood Transfusion in Critical Care
From Vincent JL et al. JAMA 288:1499-1507, 2002.
0 10 20 30 40 50 60
Transfusions (%) Pre-transfusion Hb (g/dl)
Acute bleeding 55
Physiologic reserves
Altered tissue perfusion
CAD
Other indications
28
17
8
11
P VdL
Risks associated with anemia
Risks associatedwith
blood transfusion
Effectivenessof
blood transfusion
P VdL
Patient Outcome With Very Low Hb Level
Retrospective cohort studySurgery from 1981 to 1994Postop Hb level: 8 g/dl or less
1° outcome: 30-day mortality2° outcome: 30-day morbidity
From Carson JL et al. Transfusion 42:812-818, 2002.
0
2
4
6
8
10
12
9,4
7,46,6
1,2 1,6
Complications (%)
Congestive heart failureArrhythmiaPneumoniaWound infectionMyocardial infarction
P VdL
Postoperative Hb (g/dl)
30-day mortality or morbidity (%)0 20 40 60 80 100
9,4
22
28,6
57,7
52,6
91,7
7.1 - 8.0
6.1 - 7.0
5.1 - 6.0
4.1 - 5.0
3.1 - 4.0
2.1 - 3.0
From Carson JL et al. Transfusion 42:812-818, 2002.
Patient Outcome With Very Low Hb Level
P VdL
Patient Outcome With Very Low Hb Level
Retrospective cohort studySurgery from 1981 to 1994Postop Hb level: 8 g/dl or less
1° outcome: 30-day mortality2° outcome: 30-day morbidity
From Carson JL et al. Transfusion 42:812-818, 2002.
0
2
4
6
8
10
12
9,4
7,46,6
1,2 1,6
Complications (%)
Congestive heart failureArrhythmiaPneumoniaWound infectionMyocardial infarction
After adjusting for age, CVD,& APACHE II score,the OR of death for each gram decrease Hb
was 2.1 (95% CI 1.7-2.6)
P VdL
Hemoglobin and Surgical Outcome
Independent predictor of mortality
Sepsis
Bleeding + Hb < 4.0 g/dL
Hb when <3.0 g/dL
Probability of survival less than 1% if Hb <3.0 g/dL + O2ER > 50%
O2ER (%)0
10
20
30
40
50
Alive (N=29) Dead (N=18)
From Spence RK et al. Am Surg 58(2): 92-95, 1992.
P VdL
Anemia, Cardiovascular Disease (CVD), and Surgical Mortality
Adjusted odds ratio for mortality by CVD and preop Hb
Preoperative hemoglobin (g/dl)
From Carson JL et al. Lancet 348:1055-1060, 1996.
16
13
10
7
4
16 7 8 9 10 11 12+
1981-1994
All surgeries except open-heart procedures (N=1958)
No CVD CVD
P VdL
No CVD
CVD
0 20 40 60 80 100
9,8
7,1
22,5
20
23,5
40
50
75
42,9
80
88,9
100
Postoperative Hb (g/dl)
30-day mortality or morbidity (%)
From Carson JL et al. Transfusion 42:812-818, 2002.
Patient Outcome With Very Low Hb Level
7.1 - 8.06.1 - 7.05.1 - 6.04.1 - 5.03.1 - 4.02.1 - 3.0
7.1 - 8.06.1 - 7.05.1 - 6.04.1 - 5.03.1 - 4.02.1 - 3.0
P VdL
Observational study
Healthy volunteers (N=9: 29 ± 5 years)
Verbal memory & standard computerized neuropsychologic tests:
Before and after acute isovolemic hemodilutionAfter re-transfusion of autologous bloodOn a separate day, wirhout alteration of hemoglobin
Isovolemic Anemia and Human Cognitive Function
From Weiskopf RB et al. Anesthesiology 92:1646-52, 2000.
P VdL
Isovolemic Anemia and Human Cognitive Function
60
40
20
0
-20
40
20
0
-20
7.2 6.0 5.1 7.2
40
20
0
-20
7.2 6.0 5.1 7.2
40
20
0
-20
Hemoglobin (g/dL)Hemoglobin (g/dL)
Horizontal addition (% changes) Immediate memory (% changes)
Digit-symbol substitution (% changes) Delayed memory (% changes)
From Weiskopf RB et al. Anesthesiology 92:1646-52, 2000.
****
** **
*
*p<0.05 vs Hb 14 g/dL
P VdL
Influence of Hemodilution on Outcome After Hypothermic Cardiopulmonary Bypass
Score
140
120
100
80
60
PsychomotorDev index(N=109)
MentalDev index(N=112)
p=0.008 p=0.36
From Jonas RA et al. J Thorac Cardiovasc Surg 126:1765-1774, 2003.
RCT: infants < 9 months- Hct 21.5 ± 2.9 % (N=74)- Hct 27.8 ± 3.2 % (N=73)
Blood product use: similarFluid balance:519 ± 343 vs 337 ± 222 ml p<0.001
60 min after CPBLower nadir CIHigher lactate
in the low hct group
P VdL
O2 ExtractionCardiac Output
Tissue O2 Demand
Acute Normovolemic Anemia
P VdL
Hematocrit Variations:Coronary Hemodynamics and O2 Utilization
From Jan K-M and Chien S. Am J Physiol 233:H106-H113, 1977. P VdL
Decreased cardiac output response
- hypovolemia- altered myocardial function- coronary artery disease- valvular disease...
Decreased O2ER response - impaired regional distribution of blood flow- microvascular disturbances- left shift of the O2Hb dissociation curve
Arterial hypoxemia - altered pulmonary gas exchange
Increased tissue O2 demand - hypermetabolic processes- stress, pain- emergence from sedation- rewarming- chest physiotherapy
Factors That May Reduce Patient's Tolerance to Anemia
P VdL
Risks associated with anemia
Risks associatedwith
blood transfusion
Effectivenessof
blood transfusion
P VdL
Transfusion Triggers: a Systematic Review
10 randomized trials comparing the effects of "liberal" vs
"restrictive" transfusion strategy based on a specified
hemoglobin (or hematocrit) concentration on short-term
outcome (N=1780 patients)
Surgical patients (N=5)
Acute blood loss (N=3)
ICU patients (N=2)
Transfusion triggers: hemoglobin between 7 and 10 g/dl
From Carson JL et al. Transfus Med Rev 16:187-199, 2002.
P VdL
Transfusion Triggers: a Systematic Review
In the restrictive groups:
Probability to receive a transfusion reduced by 42% (RR 0.58:
0.47-0.51)
volume of red cell transfused reduced by 0.93 units (0.36 - 1.5)
Mortality, morbidity, rates of cardiac events and length of
hospital stay unaffected by the transfusion strategy
From Carson JL et al. Transfus Med Rev 16:187-199, 2002.
P VdL
Blood Transfusion and The Heart
Systematic review of studies evaluating transfusion trigger10 studies, 1780 patients
Patients with cardiovascular disease: N=892
From Carson JL et al. Transfus Med Rev 16:187-199, 2002.
Using meta-analytic techniques, there were no differences in the combined odds ratio of death or cardiac eventsusing restrictive strategiescompared with more liberal approaches
P VdL
Blood Transfusion and The Heart
Retrospective analysis (N=78974)Blood transfusion decreased 30-day mortality in elderly patients
with a primary diagnosis of AMIif their admission hematocrit was less than 33%(Wu WC et al. N Engl J Med 345:1230-1236, 2001)
Observational study using prospectively collected data (N=24111)Blood Transfusion in the setting of acute coronary syndrome is not associated
with improved survival when nadir hematocrit values are 20-25%(Rao SV et al. JAMA 292:1555-1562, 2004)
P VdL
Effects of Blood Transfusion on Survival
From Lackritz EM et al. Lancet 340:524-528, 1992.
1.0
0.8
0.6
0.4
0.2
00 1 2 3 4 5
Probability of mortality
Admission hemoglobin (g/dl)
Transfused on day of admission vs not transfused
Threshold Hb: 3.9 g/dl
For Hb< 3.9 g/dl For Hb> 3.9 g/dl
n=194 n=149OR: 0.30 (0.14-0.61) OR: 1.88 (0.51-6.84)
P VdL
Blood Transfusion For Severe Anemic Children
Observational study (N=9968)Severely anemic children: 13%
Transfused: 65% (984/1516)
Mortality (multiple logistic regression)prostration OR: 7.4 (4.2-13.1)respiratory distress: OR: 4.1 (2.2-7.4)profound anemia: OR: 2.5 (1.4-4.5)
blood transfusion: OR: 0.28 (0.15-0.53)
0
20
40
60
80
10089
23
Mortality (%)
Not transfused Transfused
Children with prostration,respiratory distress and
Hb < 4 g/dl
From English M et al. Lancet 359:494-495, 2002.
p=0.0002
P VdL
Transfusion Strategy in Preterm Infants
Preterm infants with birth weight 500-1300 gExclusion criteria
Congenital heart disease or major birth defect requiring surgeryAllo-immune hemolytic diseaseChromosomic abnormalityImminent death
Subjects stratified by birth weight (500-750g; 751-1000g; 1001-1300g)
From Bell EF et al. Pediatrics 115:1685-1691, 2005.
P VdL
Within each birth weight stratum, infants were assigned randomly to the liberal or the restrictive transfusion group.The transfusion threshold consisted of 3 steps according to clinical condition based on respiratory status
Liberal Restrictive
Tracheally intubated for assisted ventilation 46% 34%
Nasal CPAP or supplemental O2 38% 28%
Neither positive pressure, nor O2 30 % 22 %
From Bell EF et al. Pediatrics 115:1685-1691, 2005.
Transfusion Strategy in Preterm Infants
P VdL
From Bell EF et al. Pediatrics 115:1685-1691, 2005.
Transfusions (nb)
Donor exposure
No transfusion (%)
Age at 1st transfus
0 2 4 6 8 10 12 14
Liberal Restrictive
p=0.006
Transfusion Strategy in Preterm Infants
P VdL
From Bell EF et al. Pediatrics 115:1685-1691, 2005.
Transfusion Strategy in Preterm Infants
Intravent hhageor periventricular
leukomalacia
Subjects with> 1 apnea / day
0
10
20
30
40
50
0
20
12
43
p=0.012
p=0.017%
Liberal Restrictive
Beforetransfusion
Aftertransfusion
0,4
0,6
0,8
1
1,2
1,4
1,6
Apnea episodes in 24 hours
NS
p=0.003
P VdL
Effects of Allogeneic Blood Transfusion on VO2
17 studies
Sepsis - septic shock: N=9
blood transfusion increases VO2: 2 studies
Acute respiratory failure: N=4
blood transfusion increases VO2: 2 studies
Postoperative - post-trauma: N=4
blood transfusion increases VO2: 1 study
P VdL
RBC Transfusion Increases DO2 but not VO2
No O2 deficit
Whole body VO2 measurements
Methodological problems
Changes in tissue O2 demand
Indirect vs direct VO2 measurements
Microcirculatory alterations
Abnormal RBC function
P VdL
Blood Transfusion: "Storage Effects"
Decreased 2, 3 - diphosphoglycerate (~ 0 after 15 days)Increased affinity of hemoglobin for oxygen
Decreased in red blood cell ATPchange in RBC shape (discoid to spherocytic)
reduced cellular deformability
Decreased tissue oxygen availability
endothelial swelling and tissue edema in sepsisreduce capillary luminal diameter
P VdL
Double-blind RCT
Euvolemic anemic (8.5 ± 0.8 g/dl) critically ill patients
LD RBC transfusion: 2 U
- "fresh" blood: 2 days (2 - 3); N=10
- "old" blood: 28 days (22 - 32); N=12
No difference in any globaloxygenation parameters
RBC Transfusion and Tissue Oxygenation: Effects of Storage Time
From Walsh TS et al. Crit Care Med 32:364-371, 2004.
PgCO2 -PaCO2(kPa)
pHi
Lactate(mM/l)
-1 -0,5 0 0,5 1
RBC< 5 days
RBC > 20 days
P VdL
"Fresh" Vs "Old" RBC Transfusion in Cardiac Surgery
Double-blind multicenter randomized controlled pilot studyBlood transfusion:- "Fresh": median storage time: 4 days- "Old": median storage time: 19 days
Units transfused:- "Fresh": 5.5 ± 8.4 units- "Old" : 3.3 ± 3.3 units
0
5
10
15
20
25
30
35
27
13
Death or life-threatening complication (%)
"Fresh" (N=26) "Old" (N=31)
Overall, 73% of patients received RBCs with storage times thatcorresponded to the treatment allocation more than 90% of the time
Hébert PC et al. Anesth Analg 100:1433-8, 2005.
P VdL
Preoperative Optimization of DO2 in Major Elective Surgery
RCT with double blinding between treatment groups
Treatment groups:Invasive monitoringFluids (PAOP 12 mmHg)Hb > 11 g/dlSaO2 > 94%Adrenaline or Dopexamine for DO2 >600 ml/min.m
0 20 40 60 80 100 1200
100
90
80
Survival (%)
Days after surgery
Adrenaline
Dopexamine
Control
Fisher's test for combined treatmentgroups vs control p=0007
2
N=138
From Wilson J et al. BMJ 318:1099-103,1999.P VdL
Early Goal-Directed Therapy (EGDT) in The Treatment of Severe Sepsis and Septic Shock
Treatment before ICU admission: (6 h)
Control (N =133)EGDT (N= 130)
EGDT patients (7-72 h interval):higher ScvO2
lower lactatelower base deficitlower APACHE II scores
in-hospital 28-day 60-day0
10
20
30
40
50
60
70
46,549,2
56,9
30,533,3
44,3
Mortality (%)
Control EGDT
p=0.009p=0.01
p=0.03
From Rivers E et al. N Engl J Med 345:1368-1377, 2001.P VdL
Supplemental O2 - mechanical ventilationCentral venous & arterial cathetterization
Sedation - paralysis (if intubated) or both
CVP
MAP
ScvO2
Goals achieved
ICU admission
8 - 12 mm Hg
65 - 90 mm Hg
> 70%
< 8 mm Hg
< 65 mm Hg> 90 mm Hg
< 70%RBC transfusion for hct > 30%Inotropic agents
Crystalloids - colloids
Vasoactice agents
Early Goal-Directed Therapy (EGDT) in The Treatment of Severe Sepsis and Septic Shock
From Rivers E et al. N Engl J Med 345:1368-1377, 2001.
No Yes
P VdL
TRANSFUSION MEDICINEGoodnough LT et al, NEJM 340:438-444,1999.
"It is unlikely that any level of hemoglobin can be used as a universal threshold for transfusion.
The advent of a very safe blood supply suggests that outcomes should now be monitored to identify
patients in whom transfusion may be underused in addition to identifying patients who receive
unnecessary transfusions."
P VdL
Transfusion Triggers
Dyspnea
Tachycardia
Hypotension
ST-T Abnormalities
PvO2, SvO2, O2ER
Others (lactate) ?
Central venous O2 saturation ?
P VdL
Transfusion Triggers:Logistical & Geographical Factors
Logistical factors
Available monitoring
Knowledge and availability of physician and nurse staff
Time required for blood products to be delivered
Safety of local transfusion services
Geographical factors:
high vs medium and low HDI countries
P VdL
Perioperative Transfusion Trigger
Transfusion (%)
100
0> 30%Hematocrit< 20%
Preoperative periodDefinition of anemiaSurgical riskPatient's clinical status
Peroperative periodVolemiaBlood lossesHemodynamic response
Postoperative periodMetabolic needsComplications
Logistical and geographical factors
Adapted from Janvier G et Annat G. Ann Fr Anesth Réanim 14:9-20, 1995.
P VdL
Conclusions
Humans exhibit a high tolerance to acute anemia, providing that "normovolemia" is maintained.
It is unlikely that any level of hemoglobin can be used as a universal threshold for transfusion.
Don't treat numbers, but patients using the available monitoring AND your clinical judgment
P VdL
Blood Transfusion Requirements
Red Cell Transfusion Strategies
Administer transfusion(s) on a unit-by-unit basis
Evaluate the patient after each unit
Standardized multidisciplinary approach!!!
P VdL