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