O2 to the tissues: Mission accomplished ? of tissue perfusion : • Blood pressure • Cardiac...
Transcript of O2 to the tissues: Mission accomplished ? of tissue perfusion : • Blood pressure • Cardiac...
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O2 to the tissues:Mission accomplished ?
Daniel De BackerDepartment of Intensive CareErasme University Hospital
Brussels, Belgium
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DDB USI
Determinants of tissue perfusion :
• Blood pressure• Cardiac output• Regional blood flow• Microcirculation
O2 to the tissues:Mission accomplished ?
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DDB USI
Determinants of tissue perfusion :
• Blood pressure• Cardiac output• Regional blood flow• Microcirculation
O2 to the tissues:Mission accomplished ?
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Microvascular alterations may persist even when global hemodynamic variables are within goals!
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What is the microcirculation ?
Vessels of size smaller than 100 µm
• Arterioles 100 – 20 µm• Capillaries 25 – 5 µm• Venules 20 – 100 µm
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Kerger H et alAJP 270:H827;1996
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SPECIFICITIES OF THE MICROCIRCULATION
• Primary site of gas and nutrient exchange
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Swain-D et alAJP 256:H247;1989
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Trzeciak et alCrit Care 9:S20;2005
The density of capillaries is a primary determinant of tissue oxygenation
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Saldivar-E et alAJP 285:H2064;2003
The density of capillaries is a primary determinant of tissue oxygenation
Adaptation to chronic hypoxia is characterized by an increased capillary density
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Hepple-R et alJAP 82:1305;1997
The density of capillaries is a primary determinant of tissue oxygenation
Adaptation to exercise (training) is characterized by an increased capillary density
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SPECIFICITIES OF THE MICROCIRCULATION
• Primary site of gas and nutrient exchange
• Largest endothelial surface of the body
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0
5
10³ cm²/cm³
artery
veinule
capillary (8μm)
arteriole
vein
ENDOTHELIAL SURFACE
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• Primary site of gas and nutrient exchange
• Largest endothelial surface of the body• Inflammation• Activation of coagulation
• Microcirculatory DO2 cannot be predicted from global DO2• Hematocrit lower than systemic hematocrit
(+ non linear distribution along capillaries)
SPECIFICITIES OF THE MICROCIRCULATION
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Mandatory plasma layer => hematocrit is lower is small vessels
10 µm20 µm
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Due to kinetic inertia, red blood cells will preferentially go straightforward, accordingly the hematocrit will be lower in vessels with a large angle at origin.
Cockelet et alMicrocirculation 2:1-18;1982
Hct 30
Hct 30
Hct 10
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Heterogeneity of PO2 at branchpoints
PO2 60
PO2 60
PO2 35
PO2 is lower in vicinity of vascular wall(O2 consumption by endothelium)
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Heterogeneity of PO2 at branchpointsImpact of vasoconstriction
PO2 60
PO2 60
PO2 15
PO2 is lower in vicinity of vascular wall(O2 consumption by endothelium)
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PO2 60
PO2 60
PO2 55
PO2 is lower in vicinity of vascular wall(O2 consumption by endothelium)
Heterogeneity of PO2 at branchpointsImpact of vasodilation
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• Primary site of gas and nutrient exchange
• Largest endothelial surface of the body• Inflammation• Activation of coagulation
• Microcirculatory DO2 cannot be predicted from global DO2• Hematocrit lower than systemic hematocrit
(+ non linear distribution along capillaries)• Control of blood flow under different mechanisms
SPECIFICITIES OF THE MICROCIRCULATION
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CONTROL OF MICROVASCULAR BLOOD FLOW
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MICROCIRCULATION
DDB USI
π r4 1V = Δ P
8 L η
.. . .
Determinants of microvascular blood flow
RheologyRheology Driving PressureDriving PressureConductivity
+ interaction between circulating cells and the endothelium
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Why could microvascular blood flow be altered in perioperative setting ?
• Hemorrhage• Ischemia reperfusion injury• Anesthetic agents• Surgery-induced inflammatory response• Sepsis
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DDB USI
Vascular density(all vessels)
++ p <0.01 vs volunteers
2.53
3.54
4.55
5.56
6.57n/mm
Volunteers(10)
Septic patients(50)
++
De Backer et alAJRCCM 166:98;2002
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DDB USI
Percentage of vessels perfused(large vessels)
60
65
70
75
80
85
90
95
100%
Volunteers(10)
Septic patients(50)
MICROCIRCULATORY ALTERATIONS IN SEPTIC PATIENTS
De Backer et alAJRCCM 166:98;2002
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DDB USI
0
20
40
60
80
100
Volunteers(10)
Severe sepsis(50)
+++
%
+++ p <0.001 vs volunteers
Percentage of vessels perfused(small vessels)
De Backer et al AJRCCM 166:98-104;2002
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Emergency department
Trzeciak et alAnn Em Med 49:1579;2007
N=26
0
0.5
1
1.5
2
2.5
3MFIscore
CTRL SEPSIS
P<0.01
A confirmatory study….
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Also in perioperative setting ?
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Thyroidectomy
No CPB
CPB
40
50
60
70
80
90
100
Pre Anesth CPB ICU ICU +2h ICU +24h
Porportion of perfused capillaries,% Surgery and anesthesia ?
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Surgery and anesthesia ?
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Heterogeneity of perfusion alters tissue oxygenation more than a homogenously
decreased blood flow.
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O2 36 36 36 36 ml/minSvO2 60%
O2 60 60 60 60 ml/min
24 24 24 (VO2 = 96)24
Normal flow
O2 96 0 96 0 ml/min SvO2 80%
O2 120 0 120 0 ml/min
0 24 0 (VO2 = 48)24
Heterogenous flowO2 6 6 6 6 ml/min
SvO2 20%
O2 30 30 30 30 ml/min
24 24 24 (VO2 = 96)24
Low but homogenous flow
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Relationship with outcome ?
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Rats subjected to severe hemorrhagic shock (30% mortality)
DDB USI
Zhao et al.Microvasc Res 30:143;1985
MICROVASCULAR ALTERATIONS IN HEMORRHAGIC SHOCK
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Rats subjected to severe hemorrhagic shock (30% mortality)
MAP decreased to 40 mmHg (both in survivors and in non surviors)Muscle blood flow decreased by 90% (both in survivors and in non survivors)Tissue PO2 was similar in survivors and non-survivors(Tissue PO2 between 0.5-1.0 mmHg)
DDB USI
Zhao et al.Microvasc Res 30:143;1985
MICROVASCULAR ALTERATIONS IN HEMORRHAGIC SHOCK
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Rats subjected to severe hemorrhagic shock (30% mortality)
MAP decreased to 40 mmHg (both in survivors and in non surviors)Muscle blood flow decreased by 90% (both in survivors and in non survivors)Tissue PO2 was similar in survivors and non-survivors(Tissue PO2 between 0.5-1.0 mmHg)Functional capillary density was significantly higherin survivors than in non survivors (40% vs 0%)
DDB USI
Zhao et al.Microvasc Res 30:143;1985
MICROVASCULAR ALTERATIONS IN HEMORRHAGIC SHOCK
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Rats subjected to severe hemorrhagic shock (30% mortality)
MAP decreased to 40 mmHg (both in survivors and in non surviors)Muscle blood flow decreased by 90% (both in survivors and in non survivors)Tissue PO2 was similar in survivors and non-survivors(Tissue PO2 between 0.5-1.0 mmHg)Functional capillary density was significantly higherin survivors than in non survivors (40% vs 0%)
=> only microcirculatory alterations are correlated with outcome. This points out the pivotal role of capillaries to provide O2 and nutrients to the tissues
DDB USI
Zhao et al.Microvasc Res 30:143;1985
MICROVASCULAR ALTERATIONS IN HEMORRHAGIC SHOCK
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Kerger H et alAJP 270:H827;1996
HamsterHem =>40 mmHgHatched non surv
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0
20
40
60
80
100
SURVIVORS(n = 22)
NON-SURVIVORS
(n = 28)
Proportion of perfused vessels(small vessels)
++
++ p <0.01 vs survivors
%
DDB USI
SEPSIS
MICROCIRCULATORY ALTERATIONS IN SEPTIC PATIENTS
De Backer et alAJRCCM 166:98;2002
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PATIENTS
49 Patients with septic shock included during the first 24 H of the onset of shock
Measurements of the microcirculation every 24H until resolution of shock or death.
DDB USI
Role in the development of MOF ?
MICROVASCULAR ALTERATIONS IN SEPTIC SHOCK
Sakr et alCCM 32:1825;2004
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DDB USI
EVOLUTION OF MICROCIRCULATORY ALTERATIONS IN SEPTIC PATIENTS
Death after shock
ANOVAp<0.01* * *
Sakr et alCCM 32:1825;2004
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ROC curve area:
• Baseline:• APACHE II 0.74• Lactate 0.68
• Changes between day 1 and day 2:• heart rate 0.57• mean arterial pressure 0.53• CVP 0.51• PAOP 0.64• cardiac index 0.51• SvO2 0.52• DO2 0.52• VO2 0.50• Lactate 0.63• Microvascular perfusion 0.77• SOFA score 0.61
Sakr et alCCM 32:1825;2004
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• 1st SDF evaluation within 3 hours after EGDT initiation• 2nd SDF evaluation 3 to 6 hours after EGDT initiation• SOFA changes between 0 and 24 h
33 pts with septic shock
Trzeciak et alICM (in press)
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33 pts with septic shockTrzeciak et alICM (in press)
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These alterations cannot be detectedlooking at global hemodynamics and may occur when global hemodynamic goals are achieved !
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Croner et alCrit Care 10:R15;2006
Kinetics ?
Rats, CLP
Microcirculatory alterations occur earlier than global / regional blood flow alterations
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Cardiac indexMean arterial pressure
LactateSvO2
mmHg L/min.M²
% mEq/L
40
50
60
70
80
90
100
1
2
3
4
5
6
7
20
30
40
50
60
70
80
90
Septic shockSevere sepsis
p<0.01
0
2
4
6
8
10
12
Septic shockSevere sepsisDDB USI
MICROCIRCULATORY ALTERATIONS IN SEPTIC PATIENTS
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Change in cardiac index L/min.M²
Change in capillary perfusion
%DOBU 5 mcg/kg.min
05
101520253035404550
0 0.5 1 1.5 2 2.5
De Backer et alCCM 34:403;2006
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Change in arterial pressure
%
Change in capillary perfusion
mmHg
DOBU 5 mcg/kg.min
05
101520253035404550
-20 -10 0 10 20
De Backer et alCCM 34:403;2006
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0.530.640.420.560.50DPP
0.580.680.420.680.42CI
0.520.640.420.500.55MAP
Correct classifica
tion
Neg predval
Pos predval
SpecificitySensitivity
The microvascular response to fluids cannot be predicted by global hemodynamic variables
N=36
Ospina et al
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Nakajima et alCCM 34:1847;2006
Nevertheless global hemodynamic goals should be reached before trying to manipulate the microcirculation
Rats, LPS MAP 46 71 70 44 74 71 mmHg
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• Microcirculatory alterations are frequent and cannot be detected using classical monitoring tools.
• These alterations are implicated in the development of MOF and are associated with a poor outcome.
• These alterations may occur after reaching goals of global hemodynamic resuscitation.
Conclusions
• The priority is likely to first reach global hemodynamic goals and then to stress on microcirculatory alterations.
O2 to the tissues:Mission accomplished ?