Vasopressors in septic shock

Prof. Jean-Louis TEBOUL

Medical ICU Bicetre hospital

University Paris XI France

1- Why do we use vasopressors in septic shock?

2- When to start vasopressors?

3- Which therapeutic target?

4- Which first-line agent?

Questions

1- Why do we use vasopressors in septic shock?

2- When to start vasopressors?

3- Which therapeutic target?

4- Which first-line agent?

Questions

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

Hypotension

Hypoperfusion worsening

Why do we use vasopressors in septic shock?

mean arterial pressure

organ blood flow

Autoregulation of organ blood flow

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

Why do we use vasopressors in septic shock?

48 hrs

65 mmHg

48 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

Why do we use vasopressors in septic shock?

3- Correction of hypotension with a vasopressor allows improving organ perfusion

Blood lactate (meq/l)

* *

baseline 4 hrs 8 hrs

54 mmHg

73 mmHg

72 mmHg

Urine flow (ml/h)

* *

baseline 4 hrs 8 hrs 54

mmHg 73

mmHg 72

mmHg

Creatinine clearance

*

0-2 hrs 4-6 hrs

60

30

54 mmHg

72 mmHg

while CO did not change

mean arterial pressure

renal blood flow

Autoregulation of renal blood flow

54 72

1- Why do we use vasopressors in septic shock?

2- When to start vasopressors?

3- Which therapeutic target?

4- Which first-line agent?

Questions

When to start vasopressors?

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

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

20

40

60

80

100

120

140

normal

vasoplegia

low DAP

Consider vasopressors !

reflects the vascular tone

SAP

DAP

MAP

20

40

60

80

100

120

140

1- Why do we use vasopressors in septic shock?

2- When to start vasopressors?

3- Which therapeutic target?

4- Which first-line agent?

Questions

mean arterial pressure

organ blood flow

Autoregulation of organ blood flow

?

MAP : 65 mmHg

MAP : 85 mmHg

MAP : 75 mmHg

tonometry PCO2 gap

red cell velocity

capillary flow

urine output

150

100

50

13

%

Crit Care Med 2000; 28:2729-2732

*

*

*

NE dose cardiac index

SVR

150

100

50

200

%

lactate

3.1 4.7 998

*

mean arterial pressure

organ blood flow

Autoregulation of organ blood flow

increasing the MAP > 65 mmHg

would result in little benefit

Dellinger et al. Crit Care Med 2008 Hollenberg et al. Crit Care Med 2004

MAP target value : 65 mmHg

Crit Care Med 2005; 33:780 –786

Crit Care Med 2000; 28:2729-2732

more if history of hypertension

Mean arterial pressure

Organ Blood flow

mmHg

no prior hypertension

with prior hypertension

70

1- Why do we use vasopressors in septic shock?

2- When to start vasopressors?

3- Which therapeutic target?

4- Which first-line agent?

Questions

Dellinger et al. Crit Care Med 2008

Which first-line vasopressor?

Norepinephrine rather than dopamine

• because dopamine can be dangerous

Why is NE recommended as the first-line vasopressor?

• because dopamine can be dangerous

Why is NE recommended as the first-line vasopressor?

• because NE is more powerful than dopamine

32 patients randomized to: either dopamine (until 25 µg/kg/min) or norepi (until 5 µg/kg/min)

objective : to reach and maintain mean BP > 80 mmHg over 6 hours

Norepi (n=16) Dopa (n=16)

success (n=5) failure (n=11) success (n=15)

failure (n=1)

Dopa + Norepi 10 successes with

increase in urine output decrease in lactate

increase in urine output decrease in lactate

increase in urine output and decrease in lactate

Chest 1993, 103:1826-31

• because dopamine can be dangerous

Why is NE recommended as the first-line vasopressor?

• because NE is more powerful than dopamine

• because NE can increase CO despite the increased afterload

105 pts

54

76

MAP mmHg

*

34

39

SVI mL/m2

*

694

742

GEDVI mL/m2

* 13

9

PPV %

*

Why is NE recommended as the first-line vasopressor?

• because NE can increase CO despite the increased afterload

• because NE does not impair but improves organ perfusion

• because dopamine can be dangerous

• because NE is more powerful than dopamine

Norepinephrine and

renal blood flow

Urine flow (ml/h)

* *

baseline 4 hrs 8 hrs 54

mmHg 73

mmHg 72

mmHg

Creatinine clearance

*

0-2 hrs 4-6 hrs

60

30

54 mmHg

72 mmHg

while CO did not change

MAP mmHg

*

51

79

*

81

101

Sepsis Head trauma

control

after 24h NE infusion

Septic patients Head trauma patients

*

mean arterial pressure

renal blood flow

Autoregulation of renal blood flow

sepsis

mean arterial pressure

renal blood flow

Autoregulation of renal blood flow

head trauma

Norepinephrine and

microcirculation

sublingual circulation

cutaneous circulation

OPS technology No significant change

sublingual circulation

cutaneous circulation

p < 0.05

NIRS technology

NIRS technology

15 mm 15 mm

NIRS technology

Cuff deflation

Pneumatic cuff inflation

StO2 StO2

StO2 recovery slope = StO2

t

0

20

40

60

80

100

0 2 4 6 8

minutes

t

3.2

2.3

4.7 4.8

StO2 recovery slope (%/sec)

volunteers ICU controls

severe sepsis

septic shock

* *

$

0

10

20

30

40

50

60

70

80

90

100

30 90 120 150 180 60 210 240 270 300 330

Time (sec)

StO2 (%)

Pneumatic cuff inflation

Cuff deflation

Septic shock

Control

Presumed mechanism :

microvascular dysfunction that impairs

the maximal microcirculatory recruitment

in response to an ischemic (hypoxic) stimulus

MAP mmHg 54 ± 8 77 ± 9

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

StO2 recovery slope

before NE with NE

p < 0.05

(%/s)

0

10

20

30

40

50

60

70

80

90

100

30 90 120 150 180 60 210 240 270 300 330

Time (sec)

StO2 (%)

Pneumatic cuff inflation

Cuff deflation

Septic shock before NE

Septic shock with NE

Control

Why is NE recommended as the first-line vasopressor?

• because NE can increase CO despite the increased afterload

• because NE does not impair but improves organ perfusion

• because dopamine can be dangerous

• because NE is more powerful than dopamine

NE can exert beneficial effects on regional blood flows and µcirculation when the starting MAP is low.

Since critical perfusion pressure varies from pt to pt, it seems important to assess the response of microcirculation to NE

Why is NE recommended as the first-line vasopressor?

• because NE is easy to use in daily practice - short half-time (allowing easy titration of NE dose for achieving MAP target)

- no tachycardia or arrhythmias induction

• because NE can increase CO despite the increased afterload

• because NE does not impair but improves organ perfusion

• because dopamine can be dangerous

• because NE is more powerful than dopamine

1- Why do we use vasopressors in septic shock?

2- When to start vasopressors?

3- Which therapeutic target?

4- Which first-line agent?

Conclusion

Profound vasodilation and resulting hypotension

When MAP is < 65 mmHg - despite “adequate” fluid resuscitation

- or if DAP is low even if the patient has not been yet fully resuscitated

Dellinger et al. Crit Care Med 2008 Hollenberg et al. Crit Care Med 2004

MAP target value : 65 mmHg (more if prior hypertension)

Norepinephrine recommended as the first-line agent

Thank you