1. Добрый день

2. Claude Martin
Nord University Hospital
Marseilles France
(ICU and Trauma Center)

8. Septic Shock
 Absolute hypovolemia
 relative hypovolemia
 Distributive shock : area of
VD/VC
 Cardiac dysfonction
 O2 extraction abnormalities

9. CCM , 2008 , 36 , 296-327

10. CCM , 2008 , 36 , 296-327

11. Initial Resuscitation
MAP  65 mmHg
 CVP 8 - 12 mmHg
 UF  0.5 ml.kg-1.hr-1
ScvO2  70%
 SvO2  65%
GRADE 1B

12. Treatment of
Septic shock
Hemodynamic source control
managment
Antibiotics Surgery
Fluids Vaso-active drainage
agents

13. Therapeutic Targets and Tools
Vessels :
norepinephrine
epinephrine
dopamine
Volemia :
Fluid challenge
Heart :
dobutamine
norepinephrine
Rescue therapy :
Vasopressin, terlipressin
Microcirculation :
Nitroglycerin ???

14. VASOPRESSORS
Dopamine
Epinephrenine
Norepinephrine
Vasopressin
Terlipressin

15. Initial Resuscitation CCM , 2008 , 36 , 296-327
MAP  65 mmHg
 CVP 8 - 12 mmHg
 UF  0.5 ml.kg-1.hr-1
ScvO2  70%
 SvO2  65%
Grade 1B

16. •Is venous
return optimal
?????????

17. Fluid challenge
Fluid challenge
MAP
(driving force)
Venous return
and ventricular preload
SV

19. Fluid challenge
Respiratory variation under MV
Parameter threshold
SAP 10 mmHg or 9%
down 5 mmHg
PP 12-13 %
SVV 9-10%
CVP < 5 mmHg
French Consensus Conference 2005

20. Stroke Volume Variation
SV max
SV min
SV mean
SV max + SV min
SVV =
2

21. Pulse Pressure Variations
∆PP
Michard et al.
Am J Respir Crit Care Med
PPmax 2000
PPmin

22. Fluid challenge
Respiratory variation under MV
Parameter threshold
SAP 10 mmHg or 9%
down 5 mmHg
PP 12-13 %
SVV 9-10%
CVP < 5 mmHg
French Consensus Conference 2005

23. Fluid Responsiveness in Spontaneously
Breathing Patients
PP No
SVV !!!
Teboul JL 8th Int. Consensus Conference ATS/SRLF/ERS/SCC/Esicm, Paris 27-28 April 2006

24. •Passive leg raising
with > 12%
increase
in CO by PiCCO
or oesophageal Döppler

25. Vasopressors
Norepinephrine
or Dopamine

26. 32 patients randomized : dopamine (Until 25 µg/kg/min)
or norepi ( Until 5 µg/kg/min)
Objective (n=11)
success (n=5) failure : MAP > success (n=15)for failure (n=1)
80 mmHg 6h
10 to 25 µg/kg/min 25 µg/kg/min 1.5±1.2 µg/kg/min 5 µg/kg/min
increase in urine output increase in urine output
decrease in lactate decrease in lactate
10 (n=16)
Norepi (n=16)
Dopasuccess with Dopa + Norepi (25 µg/kg/min +1.7±1.8 µg/kg/min)
Chest 1993, 103:1826-31

27. Dopamine or Norepinephrine ?
93%
69%
P < 0.001
31%
7% p < O.,001
Success Failure Success Failure
Dopamine Norepinephrine
C. Martin et al Chest 1993, 103, 1826

28. Dopamine or Norepinephrine ?
Hyperdynamic septic shock
Dopamine Norepinephrine
(2.5-25 mg (0.5-5.0 mg/kg/min)
/kg/min)
16 patients 16 patients
success : 5/16 (31%) p<0.001 success : 15/16 (93%)
failure : 11/16 failure : 1/16
success : 0/1 success : 10/11
C. Martin et al Chest 1993, 103, 1826

29. Resistance to Dopamine
110 patients
 MAP < 70 mmHg with 20 mg/kg/min
60%
P < 0.001
40%
Dopa S Dopa R
Levy et al CCM 2005, 33.

30. Resistance to Dopamine
Levy et al CCM 2005, 33

31. DOPAMINE vs NOREPINEPHRINE
SOAP study
1058 pts in shock
Mortality
* *
% 50
* 50 * P<0.05
40 43 45 42
36 37
30
20
10
0
ICU 30 Days Hospital Sakr et al
Dopamine No dopamine CCM 2006

32. Dopamine for septic
shock ???
Failure of Dopamine

35. Dopamine ou noradrénaline ?
N Engl J Med 2010
De Backer et al., N Engl J Med 2010

37. 0.19 mg/Kg/min

38. Dopamine or Norepinephrine ?
Hyperdynamic septic shock
Dopamine Norepinephrine
(2.5-25 mg)
/kg/min
(0.5-5.0
16 patients mg/kg/min)
success : 5/16 (31%) p<0.001 16 patients
failure : 11/16 success : 15/16 -93%)
success : 0/1 failure : 1/16
success : 10/11
C. Martin et al Chest 1993, 103, 1826

39. % Survival
Septic Shock :
100 Norepinephrine
90
80
70
60 Norepinephrine
50
40
p < 0.0001
30
20 Martin C et al Crit Care Med
10 Other vasopressors 2000 , 28 , 2758 .
0
0 5 10 15 20 25 30 35 40 45 50
Days

44. Adrénaline ou noradrénaline ?
Noradrénaline
Adrénaline

45. Adrénaline ou noradrénaline ?
Catécholamine utilisée en première ligne
Noradrénaline Dopamine Adrénaline
158 (57%) 102 (37%) 22 (8%)

50. •Dopamine or Norepinephrine in Human Hyperdynamic Sepsis ?
700 * 200 *
190
650
* DO2
180
VO2
600 170
160
*
550 H0 150 H0
H6 H6
140
500
130
450 120
110
400
NE Dopa 100
*
NE Dopa
7,3
7,25
* pHi
7,2
H0
7,15 H6
7,1
Marik JAMA
1994 , 272 , 1354
7,05
NE Dopa

52. Effects of Norepinephrine
on Renal Function
200 250
180
160 200
140
120 150
100 Before NE
Before NE 100 During NE
80 During NE
60 50
40
20 0
Urine Serum Creat
0 flow creat clear
Urine flow Serum creatinine
creat clearance
Martin et al Desjars et al
1990 1989

53. Vasopressors
Epinephrine is an
alternative

54. CATS Study
(Epinephrine / norepi-dobu)
Epinephrine Norepi-dobu
n = 161 (n = 169)
Hospital survival Hospital survival
47.8% 51.5%
Power 90% p = 0.51
D. Annane et al Lancet 2007

56. Metaraminol ?
 Norepinephrine treated patients switched to
metaraminol (NE : 0.3 + 0.28 µg/kg/min, Meta :
2.5 + 1.7 µg/kg/min)
= MAP = CI
(70/71) (3.7/3.6)
= SvO2
(72/72)
Natalini et al ICM 2005, 31, 634-637

59. In
case of
failure ???

60. a1-AR AC AC
a
b g
a
Gs protein
b g
P P P
Receptor
arrestin
resensitization
clathrin
Receptor endosome Receptor
internalization Receptor degradation
dephosphorylation

61. AVP

62. Vasopressors
Vasopressin :
no recommendation
 Avoid high-dose
2B

64. Norepinephrine > 15 mcg/min

65. Norepinephrine 5-14 mcg/min

69. Terlipressin?  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
MAP CI l/min/m2
mmHg 5.3+/-1.2
84+/- 6
4.7+/-1.3
55+/- 5 P< 0.01
NE + dopa TER NE + dopa TER
1147+/-134
SVRI dyn.sec 654+/-108
.cm-5.m-2
NE + dopa TER
Leone,, Martin Shock 2004,22,3146319

70.  15 patients with catecholamine - resistant
Terlipressin ? septic shock: NE ( 2.2 mcg/kg/min )
dopamine ( 25 mcg/kg/min )
Terlipressin 1 or 2 bolus of 1 mg
UF ml/h 76+/-21 Cr Cl
ml/min 47+/-36
15+/-12 21+/-15
baseline TER baseline TER
Leone,, Martin Shock 2004,22,3146319

71. Survival
?

72. Terlipressin:
Rescue Therapy

73. MAP :
65-75-85
mmHg ???

74. 150 Renal Blood Flow
Renal Autoregulation
(% baseline) in Disease
Control
3 weeks
100
1 week
50
0 20 40 60 80 100
Renal Artery Pressure (mmH g)

75. 150 Renal Blood Flow
Renal Autoregulation
(% baseline) in Disease
Control
3 weeks
100
1 week
50
0 20 40 60 80 100
Renal Artery Pressure (mmH g)

76. 150 Renal Blood Flow
Renal Autoregulation
(% baseline) in Disease
Control
3 weeks
100
1 week
50
0 20 40 60 80 100
Renal Artery Pressure (mmH g)

77. 150 Renal Blood Flow
Renal Autoregulation
(% baseline) in Disease
Control
3 weeks
100
1 week
50
0 20 40 60 80 100
Renal Artery Pressure (mmH g)

78. 65 85

79. Lactate
Increasing MAP ?
65 DO2
85
VO2
A Bourgoin et al
CCM 2005,33,780-786

80. UF
Increasing MAP ?
65 Creatinine
85
Cr Cl
A Bourgoin et al
CCM 2005,33,780-786

83. Conclusions :
Prefere norepinephrine
Dopamine ???????
Epinephrine 2 nd line
Vasopressin and terlipressin :
rescue therapy
Have a protocol

84. Спасибо