O2 to the tissues: Mission accomplished ? of tissue perfusion : • Blood pressure • Cardiac output • Regional blood flow • Microcirculation O2 to the tissues: Mission accomplished

O2 to the tissues:Mission accomplished ?

Daniel De BackerDepartment of Intensive CareErasme University Hospital

Brussels, Belgium

DDB USI

Determinants of tissue perfusion :

• Blood pressure• Cardiac output• Regional blood flow• Microcirculation


DDB USI

Determinants of tissue perfusion :

• Blood pressure• Cardiac output• Regional blood flow• Microcirculation


Microvascular alterations may persist even when global hemodynamic variables are within goals!

What is the microcirculation ?

Vessels of size smaller than 100 µm

• Arterioles 100 – 20 µm• Capillaries 25 – 5 µm• Venules 20 – 100 µm

Kerger H et alAJP 270:H827;1996

SPECIFICITIES OF THE MICROCIRCULATION

• Primary site of gas and nutrient exchange

Swain-D et alAJP 256:H247;1989

Trzeciak et alCrit Care 9:S20;2005

The density of capillaries is a primary determinant of tissue oxygenation

Saldivar-E et alAJP 285:H2064;2003


Adaptation to chronic hypoxia is characterized by an increased capillary density

Hepple-R et alJAP 82:1305;1997


Adaptation to exercise (training) is characterized by an increased capillary density



• Largest endothelial surface of the body

0

5

10³ cm²/cm³

artery

veinule

capillary (8μm)

arteriole

vein

ENDOTHELIAL SURFACE


• 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)


Mandatory plasma layer => hematocrit is lower is small vessels

10 µm20 µm

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

Heterogeneity of PO2 at branchpoints

PO2 60

PO2 60

PO2 35

PO2 is lower in vicinity of vascular wall(O2 consumption by endothelium)

Heterogeneity of PO2 at branchpointsImpact of vasoconstriction

PO2 60

PO2 60

PO2 15


PO2 60

PO2 60

PO2 55


Heterogeneity of PO2 at branchpointsImpact of vasodilation


• 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


CONTROL OF MICROVASCULAR BLOOD FLOW

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

Why could microvascular blood flow be altered in perioperative setting ?

• Hemorrhage• Ischemia reperfusion injury• Anesthetic agents• Surgery-induced inflammatory response• Sepsis

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

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


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

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….

Also in perioperative setting ?

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 ?

Surgery and anesthesia ?

Heterogeneity of perfusion alters tissue oxygenation more than a homogenously

decreased blood flow.

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

Relationship with outcome ?

Rats subjected to severe hemorrhagic shock (30% mortality)

DDB USI

Zhao et al.Microvasc Res 30:143;1985

MICROVASCULAR ALTERATIONS IN HEMORRHAGIC SHOCK


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




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




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



Kerger H et alAJP 270:H827;1996

HamsterHem =>40 mmHgHatched non surv

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



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

DDB USI

EVOLUTION OF MICROCIRCULATORY ALTERATIONS IN SEPTIC PATIENTS

Death after shock

ANOVAp<0.01* * *


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


• 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)

33 pts with septic shockTrzeciak et alICM (in press)

These alterations cannot be detectedlooking at global hemodynamics and may occur when global hemodynamic goals are achieved !

Croner et alCrit Care 10:R15;2006

Kinetics ?

Rats, CLP

Microcirculatory alterations occur earlier than global / regional blood flow alterations

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


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

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

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

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

• 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.


Documents

O2 to the tissues: Mission accomplished ? of tissue perfusion : • Blood pressure • Cardiac output • Regional blood flow • Microcirculation O2 to the tissues: Mission accomplished