microcirculatory alterations: potential mechanisms and ... backer... · microcirculatory...
TRANSCRIPT
![Page 1: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/1.jpg)
Daniel De Backer
Department of Intensive Care
Erasme University Hospital
Brussels, Belgium
MICROCIRCULATORY ALTERATIONS:
POTENTIAL MECHANISMS AND
IMPLICATIONS FOR THERAPY
![Page 2: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/2.jpg)
Microcirculatory DO2 cannot be predicted from global DO2
• Hematocrit lower than systemic hematocrit
(+ non linear distribution along capillaries)
Specificities of the microcirculation
![Page 3: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/3.jpg)
Mandatory plasma layer => hematocrit is lower is small vessels
10 µm 20 µm
![Page 4: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/4.jpg)
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 al
Microcirculation 2:1-18;1982
Hct 30
Hct 30
Hct 10
![Page 5: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/5.jpg)
Heterogeneity of PO2 at branchpoints
PO2 60
PO2 60
PO2 35
PO2 is lower in vicinity of vascular wall
(O2 consumption by endothelium)
![Page 6: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/6.jpg)
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
![Page 7: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/7.jpg)
MICROCIRCULATION
DDB USI
r4 1V = P
8 L
.
. . .
Determinants of microvascular blood flow
Blood flow is adapted to local metabolic
needs through local vasodilation and
upstream changes in vasomotor tone
![Page 8: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/8.jpg)
Neural control
Hungerford-JE et al
FASEB 14:197;2000
Perivascular
sympathetic
nerves
10 µm
![Page 9: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/9.jpg)
Neural control Beach-JM et al
AJP 275:H1489;1998
Fluorescence reflects activation
Forward and backward
transmission in response to
focal stimulation (Ach of PE)
![Page 10: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/10.jpg)
Neural control Beach-JM et al
AJP 275:H1489;1998
Arteriole
Capillaries
![Page 11: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/11.jpg)
MICROVASCULAR ALTERATIONS
IN EXPERIMENTAL SEPSIS
![Page 12: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/12.jpg)
Wang Z et al
Shock 35,141;2011
Mice / CLP LPS
IMPAIRED RENAL MICROCIRCULATION IN
EXPERIMENTAL SEPSIS
![Page 13: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/13.jpg)
Increase heterogeneity of renal perfusion in sepsis
Rats
LPS
Legrand et al
ICM 2011
![Page 14: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/14.jpg)
EXPERIMENTAL STUDIES IN SEPSIS
Microvascular blood flow alterations are frequent
decreased vascular density
absent or intermittent flow in capillaries
heterogeneity between areas
DDB USI
Branemark et Urbaschek Angiology 18:667;1967
Lam et al. JCI 94: 2077; 1994
Farquhar et al. J Surg Res 61: 190; 1996
Madorin et al CCM 27:394;1999
Ellis et al AJP 282:H156;2002
Verdant et al CCM 37:2875;2009
Secor et al ICM 2010
Different models (LPS, CLP, live bacteria,…)
Various species (rats, mice, hamsters, pigs, sheep…)
Various organs (skin, gut, liver, lung, kidney, heart, brain…)
![Page 15: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/15.jpg)
ALSO IN HUMANS ?
![Page 16: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/16.jpg)
![Page 17: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/17.jpg)
![Page 18: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/18.jpg)
DDB USI
Vascular density
(all vessels)
++ p <0.01 vs volunteers
2.5
3
3.5
4
4.5
5
5.5
6
6.5
7n/mm
Volunteers
(10)
Septic patients
(50)
++
De Backer et al
AJRCCM 166:98;2002
![Page 19: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/19.jpg)
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 al
AJRCCM 166:98;2002
![Page 20: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/20.jpg)
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
![Page 21: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/21.jpg)
Emergency department
Trzeciak et al
Ann Em Med 49:1579;2007
N=26
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
Heterogeneity index
CTRL SEPSIS
P<0.01
![Page 22: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/22.jpg)
DDB USI
EVOLUTION OF MICROCIRCULATORY ALTERATIONS IN SEPTIC PATIENTS
Death after shock
ANOVA
p<0.01* * *
Sakr et al
CCM 32:1825;2004
49 pts with septic shock
![Page 23: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/23.jpg)
Alterations of sublingual
microcirculation in patients
with sepsis
• De Backer et al AJRCCM 2002
• Spronk et al Lancet 2002
• Sakr et al CCM 2004
• De Backer et al CCM 2006
• De Backer et al CCM 2006
• Creteur et al ICM 2006
• Boerma et al CCM 2007
• Trzeciak et al Ann Emerg Med 2007
• Sakr et al CCM 2007
• Trzeciak et al ICM 2008
• Boerma et al ICM 2008
• Dubin et al Crit Care 2009
• Buchele et al CCM 2009
• Boerma et al CCM 2010
• Ospina et al ICM 2010
• Spanos et al Shock 2010
• Pottecher et al ICM 2010
• Morelli et al Crit Care 2010
• Ruiz et al Crit Care 2010
• Dubin et al J Crit Care 2010
• Morelli et al ICM 2011
• ↓ total vascular density
• ↓ perfusion of capillaries
(no flow or intermittent flow)
• Preserved venular perfusion
• Heterogeneity between areas
( close by a few microns)
![Page 24: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/24.jpg)
Potential mechanisms ?
![Page 25: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/25.jpg)
PATHOPHYSIOLOGY OF
MICROVASCULAR ALTERATIONS
Triggered by inflammatory mediators
TNF (Vicaut E JCI 87:1537;1991)
![Page 26: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/26.jpg)
ENDOTHELIAL ALTERATIONS
ctrl
5 days
post LPS
Leclers J et al
CCM 28:3672;2000
rabbits
25-35%
vessels
![Page 27: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/27.jpg)
Loss of neural control Tyml-K et al
AJP 281:H1397;2001
Change in diameter
and
communication
rate (CR500)
between 500 µm
distant
microvessels
(retrograde
communication)
B: cremaster muscle (mice)
C: Endothelial microlayer
![Page 28: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/28.jpg)
Enhanced response to vasoconstrictor substances Pannen B et al
AJP 26:180;2001
CTRL
HEM
CTRL + ET
HEM + ET
Rats
![Page 29: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/29.jpg)
2 µm
Endothelial
cell
Glycocalyx
0.2 µm
From C Ince
GLYCOCALYX ALTERATIONS
![Page 30: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/30.jpg)
Marechal X et al
Shock 29:572;2008
Role of glycocalyx in microvascular alterations
Rats, ileum
µm
![Page 31: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/31.jpg)
Hypoxia promotes leukocyte adhesion Bartolome-S et al
Shock 29:384; 2008
Mesentery
Rats
Hypoxia (FiO2 0.1)
![Page 32: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/32.jpg)
McCuskey et al
Cardiovasc Res
32:752:1996
Rouleau
formation
Altered Red blood cell deformability
![Page 33: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/33.jpg)
Eichelbronner et al
ICM 29:709;2003
ETX promotes adhesion of RBC to endothelium
HUVEC
*
![Page 34: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/34.jpg)
Croner et al
Crit Care 10:R15;2006
Microthrombi ?
Rats, CLP
Vasoconstriction
Platelet/WBC interaction with endothelium
Microthrombi not frequent
![Page 35: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/35.jpg)
Secor et al
ICM 36:1928; 2010
Mice, CLP
![Page 36: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/36.jpg)
De Backer et al
Annals Intensive Care 2011
![Page 37: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/37.jpg)
Cardiomyocytes rats
Bateman et al
AJP 293/H448;2007
CTRL LPS
Consequences…
![Page 38: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/38.jpg)
O2 40 25 65 40 ml/min
SvO2 71%
O2 60 30 90 60 ml/min
15 25 20 (VO2 = 80) 20
Normal moderately heterogenous (and adapted) flow
O2 100 0 95 0 ml/min SvO2 75%
O2 120 0 120 0 ml/min
0 25 0 (VO2 = 45) 20
Increased heterogeneity in flow
O2 10 0 20 10 ml/min
SvO2 33%
O2 30 15 45 30 ml/min
15 25 20 (VO2 = 80) 20
Low but relatively homogenous flow
![Page 39: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/39.jpg)
• Decreased total vascular density
• Decreased perfusion of capillaries
(no flow or intermittent flow)
• Preserved venular perfusion
• Heterogeneity between areas
( close by a few microns)
De Backer et al
AJRCCM 166:98-104;2002 Trzeciak et al
Ann Em Med 49:1579;2007
Spronk et al
Lancet 360:1395;2002
HOW TO TREAT MICROVASCULAR ALTERATIONS?
Therapy should aim at recruiting the
microcirculation more than at increasing flow
![Page 40: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/40.jpg)
20
30
40
50
60
70
80
90
100
Baseline Fluids
Late stage
(>48h)
N=23
Early stage
(<24h)
N=37
Proportion of perfused small vessels
%
$ p<0.01 fluids vs baseline and + p<0.01 late vs early
+ $
Microvascular effects of fluid challenge in patients with septic shock
Ospina et al
ICM 35:949;2010
![Page 41: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/41.jpg)
Baseline capillary perfusion, %
De
lta
ca
pilla
ryp
erf
us
ion
, %
EFFECTS OF RED BLOOD CELL TRANSFUSIONS
N=35
Sakr et al
CCM 35:1639;2007
![Page 42: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/42.jpg)
Capillary Perfusion
Dobutamine 5 mcg/kg.min De Backer et al
CCM 34:403;2006
21 patients in septic shock
![Page 43: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/43.jpg)
0
20
40
60
80
100
120
MAP (mmHg)
Vasodilation
Ctrl
Vasoconstiction
![Page 44: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/44.jpg)
Heterogeneity of Hct / PO2 at
branchpoints
PO2 60
PO2 60
PO2 15
Impact of
vasoconstriction
Hct 28
Hct 28
Hct 5
Decrease in Hct with vasoconstriction
(especially in small vessels)
![Page 45: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/45.jpg)
PO2 60
PO2 60
PO2 55
Heterogeneity of PO2 at branchpoints
Impact of vasodilation
Increase in Hct with vasoconstriction
(especially in small vessels)
Hct 32
Hct 32
Hct 15
![Page 46: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/46.jpg)
Friesenecker et al
AJP 287:H1792;2004
Hamster, control condition
Friesenecker et al
Crit Care 10:R75;2006
Detrimental effects in control conditions
![Page 47: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/47.jpg)
Impact of vasopressors on the microcirculation
(Norepinephrine vs Vasopressine)
Rats, LPS
Baseline value
Shock value
Nakajima et al
CCM 34:1847;2006
MAP 46 71 70 mmHg
![Page 48: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/48.jpg)
Jhanji et al
CCM 37:1961;2009
p<0.05
p=0.45
N=16
Impact of MAP/NE on microvascular perfusion
![Page 49: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/49.jpg)
Dubin et al
Crit Care 2009
N=20
Impact of MAP/NE on microvascular perfusion
![Page 50: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/50.jpg)
Dubin et al
Crit Care 2009
Impact of MAP/NE on microvascular perfusion
N=20
![Page 51: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/51.jpg)
65
70
75
80
85
90
95
100
BASE
Proportion of perfused vessels
(all vessels)
++ p <0.01 vs base
TOPICAL ACETYLCHOLINE
(10-2 M)
Patients with septic shock (n = 11)
%
DDB USI
MICROCIRCULATORY ALTERATIONS IN SEPTIC PATIENTS
De Backer et al
AJRCCM 166:98;2002
![Page 52: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/52.jpg)
Spronk et al
Lancet 360:1395;2002
Effects of nitroglycerin
8 pts with septic shock
![Page 53: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/53.jpg)
Boerma E et al
CCM 38:93-100;2010
Effects of nitroglycerin
70 pts with severe sepsis
![Page 54: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/54.jpg)
Effects of nitroglycerin
70 pts with severe sepsis
But can normal be more normal than normal ?
Boerma E et al
CCM 38:93-100;2010
![Page 55: MICROCIRCULATORY ALTERATIONS: POTENTIAL MECHANISMS AND ... Backer... · microcirculatory alterations: potential mechanisms and implications for therapy . ... ellis et al ajp 282:h156;](https://reader031.vdocuments.us/reader031/viewer/2022021822/5b169cf47f8b9a6d6d8ce2fa/html5/thumbnails/55.jpg)
• Multiple experimental and clinical studies suggest
that microvascular alterations play a key role in the
pathophysiology of sepsis and in the development of
sepsis-induced organ failure.
CONCLUSIONS
• These alterations are due to several factors
(endothelial dysfunction, interaction with circulating
cells) that make unlikely that classical hemodynamic
resuscitation can be effective in restoring an adequate
microcirculation.