Добрый день

Claude Martin

Nord University Hospital Marseilles France

(ICU and Trauma Center)

Septic Shock

Absolute hypovolemia

relative hypovolemia

Distributive shock : area of

VD/VC

Cardiac dysfonction

O2 extraction abnormalities

CCM , 2008 , 36 , 296-327

CCM , 2008 , 36 , 296-327

Initial Resuscitation

MAP 65 mmHg

CVP 8 - 12 mmHg

UF 0.5 ml.kg-1.hr-1

ScvO2 70%

SvO2 65%

GRADE 1B

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 ???

VASOPRESSORS Dopamine

Epinephrenine

Norepinephrine

Vasopressin

Terlipressin

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

•Is venous

return optimal

?????????

Fluid challenge

MAP

(driving force)

Venous return

and ventricular preload

SV

Fluid challenge

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

Stroke Volume Variation

SV max

SV min

SV mean

SV max + SV min

2

SVV =

PPmax

PPmin

∆PP Michard et al.

Am J Respir Crit Care Med

2000

Pulse Pressure Variations

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

!!!

•Passive leg raising

with > 12% increase

in CO by PiCCO

or oesophageal Döppler

Vasopressors

Norepinephrine

or Dopamine

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

Resistance to Dopamine

Levy et al CCM 2005, 33

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 for septic

shock ???

Failure of Dopamine

Dopamine ou noradrénaline ?

N Engl J Med 2010

De Backer et al., N Engl J Med 2010

0.19 mg/Kg/min

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 ?

Noradrénaline

Adrénaline

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

Vasopressors

Epinephrine is an

alternative

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

In

case of

failure ???

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

AVP

Vasopressin :

no recommendation

Avoid high-dose

Vasopressors

2 B

Norepinephrine > 15 mcg/min

Norepinephrine 5-14 mcg/min

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

Survival

?

Terlipressin:

Rescue Therapy

MAP :

65-75-85

mmHg ???

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

65 85

A Bourgoin et al

CCM 2005,33,780-786

Increasing MAP ? Lactate

DO2

VO2

65 85

Increasing MAP ? UF

Creatinine

Cr Cl

A Bourgoin et al

CCM 2005,33,780-786

85 65

Conclusions :

Prefere norepinephrine

Dopamine ???????

Epinephrine 2nd line

Vasopressin and terlipressin :

rescue therapy

Have a protocol

Спасибо