Prof. Jean-Louis TEBOULProf. Jean-Louis TEBOUL

Medical ICUBicetre hospital

University Paris-SouthFrance

Ideal MAP for resuscitationIdeal MAP for resuscitation

A moving targetA moving target

1- 1- WhyWhy do we use vasopressors in septic shock? do we use vasopressors in septic shock?

3- 3- WhenWhen to start? to start?

4- 4- WhichWhich therapeutic therapeutic targettarget??

2- 2- WhichWhich first-line first-line agentagent??

Questions

1- 1- WhyWhy do we use vasopressors in septic shock? do we use vasopressors in septic shock?

Questions

2- Which first-line agent?

3- When to start?

4- Which therapeutic target?

Septic shock is characterized by a decreased vascular toneSeptic shock is characterized by a decreased vascular tone(inducible NO synthase activation, etc)(inducible NO synthase activation, etc)

HypotensionHypotension

Hypoperfusion worseningHypoperfusion worsening

Why do we use vasopressors in septic shock?Why do we use vasopressors in septic shock?

mean arterial pressure

organ blood flow

Autoregulation of organ blood flowAutoregulation of organ blood flow

2- Profound 2- Profound hypotensionhypotension worsens worsens organ hypoperfusionorgan hypoperfusion

1- Septic shock is characterized by a decreased vascular tone(inducible NO synthase activation, etc)

…… …… and represents an and represents an independent risk of deathindependent risk of death

Why do we use vasopressors in septic shock?Why do we use vasopressors in septic shock?

65 mmHg65 mmHg

48 hrs48 hrs

2- Profound hypotension worsens organ hypoperfusion

1- Septic shock is characterized by a decreased vascular tone(inducible NO synthase activation, etc)

…… and represents an independent risk of death

3- 3- Correction of hypotensionCorrection of hypotension with a vasopressor allows with a vasopressor allows improvingimproving organ perfusionorgan perfusion

Why do we use vasopressors in septic shock?Why do we use vasopressors in septic shock?

Creatinine clearanceCreatinine clearance

**

0-2 hrs 4-6 hrs0-2 hrs 4-6 hrs

60

30

5454 mmHg

7272 mmHg

while while cardiac outputcardiac output did did not changenot change

Urine flowUrine flow (ml/h)

**

**

baseline 4 hrs 8 hrsbaseline 4 hrs 8 hrs

5454 mmHg

7373 mmHg

7272 mmHg

Blood lactateBlood lactate (meq/l)(meq/l)

****

baseline 4 hrs 8 hrsbaseline 4 hrs 8 hrs

5454 mmHg

7373 mmHg

7272 mmHg

Probable “arterial pressure” effect

mean arterial pressure

renal blood flow

Autoregulation of Autoregulation of renalrenal blood flow blood flow

54 72

2- Profound hypotension worsens organ hypoperfusion

1- Septic shock is characterized by a decreased vascular tone(inducible NO synthase activation, etc)

…… and represents an independent risk of death

3- 3- Correction of hypotensionCorrection of hypotension with a vasopressor allows with a vasopressor allows improvingimproving organ perfusionorgan perfusion

Why do we use vasopressors in septic shock?Why do we use vasopressors in septic shock?

and and microcirculationmicrocirculation

95

90

85

80

75

70

65

60

55

StO2

before NEbefore NE with NEwith NE

%

p < 0.05StOStO22: 75 : 75 ±± 9% 9%

82 82 ±± 4 * 4 *

healthyvolunteers

NIRS technologyNIRS technology

StO2 (%)

Time

End point : 0.85 x baseline StO2

Start point : 1.05 x minimal StO2

Start point :

0.98 x baseline StO2

Deflation of the pneumatic cuff

Inflation of the pneumatic cuff

Occlusion time

AUC

40

50

60

70

80

90

Desaturationslope

Vascular Occlusion Test

Index of recruitment

of microvessels

RecoveryRecoveryslopeslope

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

StO2 recovery slope

before NEbefore NE with NEwith NE

(%/s)

p < 0.05p < 0.05

Restoration of a “goodgood” MAP MAP

with early early introduction of NE NE

resulted in recruitmentrecruitment

of microvessels microvessels and better tissue oxygenation better tissue oxygenation

1- Why do we use vasopressors in septic shock?

Questions

2- Which first-line agent?

3- When to start?

4- Which therapeutic target?

1- Why do we use vasopressors in septic shock?

Questions

2- Which first-line agent?

3- When to start?

4- Which therapeutic target?

20

40

60

80

100

120

140

vasodilatationvasodilatation

low DAPlow DAP

Consider vasopressorsConsider vasopressors

reflects reflects the vascular tonethe vascular tone

SAP

DAPDAP

MAP

20

40

60

80

100

120

140

When When to startto start vasopressors? vasopressors?

• when MAP MAP is < 65 mmHg < 65 mmHg despite “adequate” fluid resuscitation

• or when MAP MAP is < 65 mmHg < 65 mmHg and DAP DAP is low low even if the patient has not been yet fully fluid resuscitated

1- Why do we use vasopressors in septic shock?

Questions

2- Which first-line agent?

3- When to start?

4- Which therapeutic target?

mean arterial pressure

organ blood flow

Autoregulation of organ blood flowAutoregulation of organ blood flow

?? 65 mmHg?

MAP:MAP: 6565 mmHgmmHg

MAP:MAP: 8585 mmHgmmHg

MAP:MAP: 7575 mmHgmmHg

tonometry PCO2 gap

red cell velocity

capillaryflow

urineoutput

150150

100100

5050

13

%%

Mean Arterial Pressure (mmHg)

organ blood flow

Autoregulation of organ blood flowAutoregulation of organ blood flow

65 75 85

Crit Care Med 2000; 28:2729-2732

Crit Care Med 2005; 33:780 –786

increasing MAP above 65 mmHg

results in little benefit

65 mmHg65 mmHg

48 hrs48 hrs

Crit Care Med 2000; 28:2729-2732

Crit Care Med 2005; 33:780 –786

MAP target value: 6565 mmHg

Probably higher target value if:

• History of chronic hypertension

MAP:MAP: 6565 mmHgmmHg

MAP:MAP: 8585 mmHgmmHg

MAP:MAP: 7575 mmHgmmHg

tonometry PCO2 gap

red cell velocity

capillaryflow

urineoutput

150150

100100

5050

13

%%

10 patientsnone with history

of severe hypertension

Mean arterial pressureMean arterial pressure

OrganOrganBloodBloodflowflow

mmHgmmHg

no prior hypertensionno prior hypertension

with prior hypertensionwith prior hypertension

6565

pts with no chronic hypertensionpts with no chronic hypertension

pts with chronic hypertensionpts with chronic hypertension

Probably higher target value if:

• History of chronic hypertension

• High CVP

Probably higher target value if:

• History of chronic hypertension

• High CVP

• Increased abdominal pressure

Is it dangerous to target a MAP value

up to “normal values” (around 85 mmHg)

in septic shock?

65 75 85 65

Reco

very

slo

pe

Reco

very

slo

pe

%/m

in%

/min

MAP MAP mmHgmmHg

****

13 pts 13 pts with septic shockwith septic shock

6 pts 6 pts with septic shockwith septic shock

Perfused Vessel Density

Microvascular Flow Index

No worsening but improvement of microcirculation

for MAP target up to 85 mmHg with NE

20 pts 20 pts with septic shockwith septic shock

Highly variable response among patients

Perfused capillary density improved in pts with an altered

sublingual perfusion at baseline, and decreased in patients

with preserved basal microvascular perfusion.

20 pts 20 pts with septic shockwith septic shock

1- Why do we use vasopressors in septic shock?

3- When to start?

4- Which therapeutic target?

2- Which first-line agent?

ConclusionConclusion

at least 65 mmHg

probably higher value if:

• History of chronic hypertension• High CVP• Increased abdominal pressure

Thank you Thank you

65-85 mmHgseems to be a safe range