Septic Shock

Absolute hypovolemia Relative hypovolemia Distributive shock :areas

of VD/VC Cardiac dysfunction Impaired O2 extraction

History of Septic Shock60’s hypotension vasopressors

normalize BP70’s Inadequate flow

measure CO + inotrope80’s Inadequate DO2

DO2/VO2 + inotrope90’s Regional circulations + dopexamine

phi, lactate + dopexamine00’s Microcirculation failure + vasodilators

« open » capillary beds

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%

BE SURETHE PATIENT

IS ADEQUATLYFLUID-

RESCUCITATED

Fluid challenge

French Consensus Conference 2005

10 mmHg or 9%5 mmHg12-13 %9-10%

< 5 mmHg

SAPdownPPSVV

CVP

thresholdParameterRespiratory variation under MV

5-6 %

00

2020

4040

6060

8080

100100

00 2020 4040 6060 8080 100100100100-- SpecificitySpecificity(%)

Sens

itivi

tySe

nsiti

vity

(%)

(%)

PPPP

SPVSPV

RAPRAP

PAOPPAOP

AmAm J J RespirRespir CritCrit Care Care MedMed 2000; 162:1342000; 162:134--88

Passive Leg Rising Predicts Response to Fluid Loading

Rapid fluid loading :300 ml, > 20 min.

Boulain, Chest 2002, 121, 1245

Fluid challenge

500 ml (7 ml/kg)(either colloid or crystalloid

20 – 30 min

Fluid Challenge and Severe Sepsis

Cristalloids Colloids

Schierhout BMJ 1998, 316, 961Wilkes Ann Int Med 2001, 135, 149Choi CCM 1999, 27, 200Sibbald www.uptodate.com 2003, 1/03

SafeStudy

NEJM 2004 , 350 , 2247-2256

Safe Study

NEJM 2004 , 350 , 2247-2256

HEA or Gelatine for Severe Sepsis ?Schortgen et al Lancet 2001 , 357 , 911

Patients without Acute Renal Failure

Gelatine

HES

HEA or Gelatine for Severe Sepsis ?Schortgen et coll Lancet 2001 , 357 , 911

Survivors

P=0.09

Subgroup Analysis

(</= 22mL/Kg/day)

(> 22mL/Kg/day)

P<0.001

Hydroxyethyl Starch

HES 200,000/0.66% solution (60g/l)Na+ 154 mmol/l12 - 24h

HES 200,000/0.56% solution (60g/l)Na+ 154 mmol/l4 - 8h

33 ml / kg / 24h

ChestChest 1993, 103:18261993, 103:1826--3131

32 patients 32 patients randomizedrandomized : dopamine: dopamine ((UntilUntil 25 25 µµg/kg/min)g/kg/min) or or norepinorepi ( ( UntilUntil 5 5 µµg/kg/min)g/kg/min)

Objectif : PAM > 80 Objectif : PAM > 80 mmHgmmHg 6 h6 h

NorepiNorepi (n=16) (n=16) Dopa (n=16) Dopa (n=16)

successsuccess (n=5)(n=5)10 to 25 10 to 25 µµg/kg/ming/kg/min

ééchec (n=11)chec (n=11)25 25 µµg/kg/ming/kg/min

successsuccess (n=15)(n=15)1.51.5±±1.2 1.2 µµg/kg/ming/kg/min

failurefailure (n=1)(n=1)5 5 µµg/kg/ming/kg/min

10 10 successsuccess withwith Dopa + Dopa + NorepiNorepi (25 (25 µµg/kg/min +1.7g/kg/min +1.7±±1.8 1.8 µµg/kg/min)g/kg/min)

increaseincrease in urine outputin urine outputdecreasedecrease in lactatein lactate

increaseincrease in urine outputin urine outputdecreasedecrease in lactatein lactate

increaseincrease in urine output in urine output andand decreasedecrease in lactatein lactate

Dopamine or Norepinephrine ?

69%P < 0.001

93%

7 % p < O. 001

Success FailuresDopamine

Success FailuresNorepinephrrine

31%

C. Martin et al Chest 1993, 103, 1826

Dopamine or Norepinephrine ?Hyperdynamic septic shock

Dopamine(2.5-25 g /kg/min)

16 patientssuccess : 5/16 (31%)

failure : 11/16success : 0/1

Norepinephrine(0.5-5.0 g/kg/min)

16 patientssuccess : 15/16 -93%)

failure : 1/16success : 10/11

C. Martin et al Chest 1993, 103, 1826

p<0.001

110 patientsMAP < 70 mmHg with 20 g/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.

Septic Shock :Norepinephrine

Martin C et al Crit Care Med2000 , 28 , 2758 .

0102030405060708090

100

0 5 10 15 20 25 30 35 40 45 50

Other vasopressors

Norepinephrine

Days

% Survival

p<0.0001

CATS Study(Epinephrine / norepi-dobu)

Epinephrinen = 161

Norepi-dobu(n = 169)

Hospital survival47.8%

Hospital survival51.5%

p = 0.51

D. Annane et al Lancet 2007,370,676-684

D. Annane et al Lancet 2007,370,676-684

MAP :65-75-85

mmHg ???

20 40 60 80 100 Renal Artery Pressure (mmH g)

Renal Blood Flow(% baseline)

150

100

50

0

Renal Autoregulationin Disease

Control3 weeks

1 week

20 40 60 80 100 Renal Artery Pressure (mmH g)

Renal Blood Flow(% baseline)

150

100

50

0

Renal Autoregulationin Disease

Control3 weeks

1 week

20 40 60 80 100 Renal Artery Pressure (mmH g)

Renal Blood Flow(% baseline)

150

100

50

0

Renal Autoregulationin Disease

Control3 weeks

1 week

20 40 60 80 100 Renal Artery Pressure (mmH g)

Renal Blood Flow(% baseline)

150

100

50

0

Renal Autoregulationin Disease

Control3 weeks

1 week

65 85

Increasing MAP ?UF

Creatinine

Cr ClA Bourgoin et alCCM 2005,33,780-786

8565

MAP :65 mmHg

Septic shock. Inotropic Therapy

. Dobutamine is the first choice for patients with low CO

< 2.5 l/min/m2after fluid resuscitationafter an adequate MAP (Level E)

. Dobutamine may cause hypotensionand /or tachycardia in some patients: especially those with low filling

pressureTask Force of the SCCM. Crit. Care Med 2004,32,1928-1948

Initial Resuscitation

MAP 65 mmHg CVP 8-12 mmHg UF 0.5 ml.kg-1.hr-1

ScvO2 70% SvO2 65%

Early « Goal-directed therapy »

Rivers et coll N Eng J Med 2001, 345, 1368-1377

3499 ml4981 ml

P < 0,001

18.5%

64.1% p < 0,001

contrôles GDTExpansion volémique

contrôles

contrôles GDT

GDT

Transfusion (% patients)

0.8%p < 0,001

13.7%

Dobutamine (% patient)

Early « Goal-directed Therapy »

Hospital mortality

46.5%30.5% (p = 0.009)

Controls GDT

Rivers et al NEJM, 2001, 345, 1368-1377

Rescue Therapy

1-AR AC AC

arrestin

endosome

P P P

clathrin

Receptorinternalization Receptor

dephosphorylation

Receptordegradation

Receptorresensitization

Gs protein

VASOPRESSIN

• Regulation of plasmaticosmolarity and volemia

• Heterogeneousvasoconstriction

Liard et al. Am J Physiol 1982

• Vasodilation in somecirculatory beds

Walker. Am J Physiol 1986

AVP

Norepinephrine > 15 mcg/min

Norepinephrine 5-14 mcg/min

Only asrescue therapy

Terlipressin?

Albanese , Martin Shock 2004,22,314-319

MAPmmHg

SVRI dyn.sec.cm-5.m-2

NE + dopa TER NE + dopa TER

TERNE + dopa

15 patients with catecholamine - resistantseptic shock: NE ( 2.2 mcg/kg/min ) dopamine ( 25 mcg/kg/min )

Terlipressin 1 or 2 bolus of 1 mgCI l/min/m2

84+/- 64.7+/-1.3

1147+/-134

55+/- 5

654+/-108

5.3+/-1.2

P< 0.01

Terlipressin?

UFml/min

Cr CL ml/min/ 1.74 m2

NE + dopa TER

TERNE + dopa

67+/- 33

49+/-37

11+/-15

17+/-44

P<0,01

P<0.01

15 patients with catecholamine - resistantseptic shock: NE ( 2.2 mcg/kg/min ) dopamine ( 25 mcg/kg/min )

Terlipressin 1 or 2 bolus of 1 mg

Albanese , Martin Shock 2004,22,314-319

Dynamic Aspect

1st hour blood gas lactate cultures ATB peripheral IV vasopressor fluid

2nd hourMAP 65 mmHg arterial line CVC SvO2 CVP > 5 mmHg

6th hour

ScvO2 > 70%SvO2 > 65 % plateau pressure

< 30 mmHg

Dynamic Aspect

1st hour

blood gas lactate cultures ATB peripheral IV vasopressor fluid

2nd hour

MAP 65 mmHg arterial line CVC SvO2 CVP > 5 mmHg

6th hour

ScvO2 > 70%SvO2 > 65 % plateau pressure

< 30 mmHg