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Septic Shock
Absolute hypovolemia
relative hypovolemia
Distributive shock : area of
VD/VC
Cardiac dysfonction
O2 extraction abnormalities
Antibiotics
Hemodynamic
managment
Treatment of
Septic shock
source control
Fluids Vaso-active
agents
Surgery
drainage
Therapeutic Targets and Tools
Volemia :
Fluid challenge
Vessels :
norepinephrine
epinephrine
dopamine
Rescue therapy :
Vasopressin, terlipressin
Heart :
dobutamine
norepinephrine
Microcirculation :
Nitroglycerin ???
Initial Resuscitation
MAP 65 mmHg CVP 8 - 12 mmHg
UF 0.5 ml.kg-1.hr-1
ScvO2 70%
SvO2 65%
Grade 1B
CCM , 2008 , 36 , 296-327
Fluid challenge
French Consensus Conference 2005
Parameter threshold
SAP
down
PP
SVV
CVP
10 mmHg or 9%
5 mmHg
12-13 %
9-10%
< 5 mmHg
Respiratory variation under MV
Fluid challenge
French Consensus Conference 2005
Parameter threshold
SAP
down
PP
SVV
CVP
10 mmHg or 9%
5 mmHg
12-13 %
9-10%
< 5 mmHg
Respiratory variation under MV
Fluid Responsiveness in Spontaneously
Breathing Patients
Teboul JL 8th Int. Consensus Conference ATS/SRLF/ERS/SCC/Esicm, Paris 27-28 April 2006
PP
SVV No
!!!
Chest 1993, 103:1826-31
32 patients randomized : dopamine (Until 25 µg/kg/min)
or norepi ( Until 5 µg/kg/min)
success (n=5)
10 to 25 µg/kg/min
failure (n=11)
25 µg/kg/min
success (n=15)
1.5±1.2 µg/kg/min
failure (n=1)
5 µg/kg/min
10 success with Dopa + Norepi (25 µg/kg/min +1.7±1.8 µg/kg/min)
increase in urine output
decrease in lactate
increase in urine output
decrease in lactate
Norepi (n=16)
Dopa (n=16)
Objective : MAP > 80 mmHg for 6 h
Dopamine or Norepinephrine ?
69%
P < 0.001
93%
7 % p < O.,001
Success Failure
Dopamine
Success Failure
31%
C. Martin et al Chest 1993, 103, 1826
Norepinephrine
Dopamine or Norepinephrine ?
Hyperdynamic septic shock
Dopamine (2.5-25 mg /kg/min) 16 patients success : 5/16 (31%) failure : 11/16 success : 0/1
Norepinephrine (0.5-5.0 mg/kg/min) 16 patients success : 15/16 (93%) failure : 1/16 success : 10/11
C. Martin et al Chest 1993, 103, 1826
p<0.001
110 patients
MAP < 70 mmHg with 20 mg/kg/min
Resistance to Dopamine
Levy et al CCM 2005, 33.
40%
Dopa S
60%
P < 0.001
Dopa R
DOPAMINE vs NOREPINEPHRINE
Sakr et al
CCM 2006
SOAP study 1058 pts in shock
36
43
37
4542
50
0
10
20
30
40
50
ICU 30 Days Hospital
No dopamine Dopamine
Mortality
% * P<0.05 *
* *
Dopamine or Norepinephrine ?
Hyperdynamic septic shock
Dopamine (2.5-25 mg) /kg/min 16 patients success : 5/16 (31%) failure : 11/16 success : 0/1
Norepinephrine
(0.5-5.0 mg/kg/min) 16 patients success : 15/16 -93%) failure : 1/16 success : 10/11
C. Martin et al Chest 1993, 103, 1826
p<0.001
Septic Shock :
Norepinephrine
Martin C et al Crit Care Med
2000 , 28 , 2758 .
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25 30 35 40 45 50
Other vasopressors
Norepinephrine
Days
% Survival
p < 0 . 0 0 0 1
Adrénaline ou noradrénaline ?
158 (57%) 102 (37%) 22 (8%)
Catécholamine utilisée en première ligne
Noradrénaline Dopamine Adrénaline
400
450
500
550
600
650
700
NE Dopa
H 0
H 6
100
110
120
130
140
150
160
170
180
190
200
NE Dopa
H 0
H 6
7,05
7,1
7,15
7,2
7,25
7,3
NE Dopa
H 0
H 6
*
*
*
*
*
*
DO2 VO2
pHi
•Dopamine or Norepinephrine in Human Hyperdynamic Sepsis ?
Marik JAMA 1994 , 272 , 1354
0
20
40
60
80
100
120
140
160
180
200
Urine flow creatinine
clearance
Before NE
During NE
Martin et al 1990
0
50
100
150
200
250
Urine
flow
Serum
creat
Creat
clear
Before NE
During NE
Desjars et al 1989
Effects of Norepinephrine on Renal Function
Serum
creat
CATS Study
(Epinephrine / norepi-dobu)
Epinephrine
n = 161
Norepi-dobu (n = 169)
Hospital survival
47.8%
Hospital survival
51.5%
p = 0.51
D. Annane et al Lancet 2007
Power 90%
Metaraminol ?
Norepinephrine treated patients switched to
metaraminol (NE : 0.3 + 0.28 µg/kg/min, Meta :
2.5 + 1.7 µg/kg/min)
= MAP
(70/71)
= CI
(3.7/3.6)
= SvO2
(72/72)
Natalini et al ICM 2005, 31, 634-637
a
g b
a1-AR AC AC
a
g b
arrestin
endosome
P P P
clathrin
Receptor
internalization Receptor
dephosphorylation
Receptor
degradation
Receptor
resensitization
Gs protein
Terlipressin?
Leone,, Martin Shock 2004,22,3146319
MAP
mmHg
SVRI dyn.sec
.cm-5.m-2
NE + dopa TER NE + dopa TER
TER NE + dopa
15 patients with catecholamine - resistant
septic shock: NE ( 2.2 mcg/kg/min )
dopamine ( 25 mcg/kg/min )
Terlipressin 1 or 2 bolus of 1 mg
CI l/min/m2
84+/- 6 4.7+/-1.3
1147+/-134
55+/- 5
654+/-108
5.3+/-1.2
P< 0.01
Terlipressin ?
UF ml/h
baseline TER baseline TER
Cr Cl
ml/min
15+/-12
76+/-21
21+/-15
47+/-36
15 patients with catecholamine - resistant
septic shock: NE ( 2.2 mcg/kg/min )
dopamine ( 25 mcg/kg/min )
Terlipressin 1 or 2 bolus of 1 mg
Leone,, Martin Shock 2004,22,3146319
20 40 60 80 100
Renal Artery Pressure (mmH g)
Renal Blood Flow (% baseline)
150
100
50
0
Renal Autoregulation in Disease
Control 3 weeks 1 week
20 40 60 80 100
Renal Artery Pressure (mmH g)
Renal Blood Flow (% baseline)
150
100
50
0
Renal Autoregulation in Disease
Control 3 weeks 1 week
20 40 60 80 100
Renal Artery Pressure (mmH g)
Renal Blood Flow (% baseline)
150
100
50
0
Renal Autoregulation in Disease
Control 3 weeks 1 week
20 40 60 80 100
Renal Artery Pressure (mmH g)
Renal Blood Flow (% baseline)
150
100
50
0
Renal Autoregulation in Disease
Control 3 weeks 1 week
Conclusions :
Prefere norepinephrine
Dopamine ???????
Epinephrine 2nd line
Vasopressin and terlipressin :
rescue therapy
Have a protocol
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