How Hight
Should MAP Be
?
C Martin MD,FCCM,FCCP
ICU and Trauma Center
Nord University Marseilles France
150 Organ Blood Flow Autoregulation
(% baseline)
100
in Health and Disease
Autoregulatory
threshold
•Below their autoregulatory
thresholds, organ flows are
linearly dependent on perfusion
pressure.
50
Subautoregulatory slope
0
20
40
60
80
Organ Artery Pressure (mmHg)
100
What about settings where
organ autoregulation is lost
?
150
Organ Blood Flow
(% baseline)
Autoregulation
in Disease
Control
3 weeks
100
1 week
50
0
20
40
60
80
100
Organ Artery Pressure (mmH g)
Any increase in organ
perfusion is likely to
augment
organ blood flow
150
Organ Blood Flow
(% baseline)
Autoregulation
in Disease
Control
3 weeks
100
1 week
50
0
20
40
60
80
Ogan Artery Pressure (mmH g)
100
Norepinephrine and Regional Blood
Flow during Hyperdynamic Sepsis
Merino ewes IV bolus of E. coli (3x109)
Norepinephrine 0.4 g/kg/min or placebo
MAP
(mmHg)
87+7 (p < 0.05)
CO
L/min
8 + 0.8 (p<0.05 )
7.2+12
69+8
Placebo NE
Placebo NE
Giantomasso ICM 2004
Norepinephrine and Regional Blood
Flow during Hyperdynamic Sepsis
CrCL
mlL/min
UF
(ml/h)
83 + 54 (p<0.05 )
117+101 p < 0.05)
41+30
52+23
Placebo NE
Placebo NE
Giantomasso ICM 2004
What is the relevance of
these experimental
studies to clinical practice
???
Norepinephrine and Renal Blood Flow
MAPressure
Urine Flow ml/h
Time
Desjars CCM 1983, 1987
Meadows CCM 1988
Time
Hesselvik CCM 1989
Martin CCM 1990
Martin Chest 1994
……….
Norepinephrine in Septic and NonSeptic Patients
Septic shock
Creatinine
Cr CL
300+137
180+110 p < 0.05
before
Creatinine
100+27
before
0.7 + 0.3
24hr
before
Head trauma
107+17
24hr
1.7+0.9 p < 0.05
24hr
Cr CL
2.8+0.7
before
2.7+ 0.6
24hr
Albanese et al Chest 2004,126,534-539
MAP :
65-75-85
mmHg ???
150
Organl Blood Flow
(% baseline)
Autoregulation
in Disease
Control
3 weeks
1 week
100
50
0
20
40
60
80
100
Organ Artery Pressure (mmH g)
150
Organ Blood Flow
(% baseline)
Autoregulation
in Disease
Control
3 weeks
1 week
100
50
0
20
40
60
80
100
Organ Artery Pressure (mmH g)
150
Organ Blood Flow
(% baseline)
Autoregulation
in Disease
Control
3 weeks
1 week
100
50
0
20
40
60
80
100
Organ Artery Pressure (mmH g)
*
5,6
5,4
*
Increasing MAP ?
5,2
5
CI
4,8
CI
10 septic shock patients
treated by NE
*
720
4,6
700
4,4
680
4,2
MAP 65
MAP 75
MAP 85
DO2
660
640
DO2
620
160
600
140
VO2
120
100
80
580
560
MAP 65
MAP 75
MAP 85
VO2
60
•LeDoux et al Crit Care Med
2000 , 28 , 2729
40
20
0
MAP 65
MA 75
MAP 85
•Increasing MAP ?
60
50
•10 septic shock patients treated by NE
40
30
UF
Urine flow 18
20
16
14
10
12
0
MAP 65
MAP 75
MAP 85
10
Pa-PiCo2
8
0,45
6
0,4
4
0,35
2
0,3
0
MAP 65
0,25
MAP 75
MAP 85
Red cell velocity
0,2
0,15
•LeDoux et al Crit Care Med
2000 , 28 , 2729
0,1
0,05
0
MAP 65 MAP 75 MAP 85
65
85
Lactate
Increasing MAP ?
65
DO2
85
VO2
A Bourgoin et al
CCM 2005,33,780-786
UF
65
Creatinine
Increasing MAP ?
85
Cr Cl
A Bourgoin et al
CCM 2005,33,780-786
MAP :
65 mmHg
Unresolved issues :
Formerly hypertensive patients ?
Elderly patients ?
Atherosclerotic patients ?
Others ????
Coronary Artery flow
Cardiogenic Shock
Management of Hypotension
SBP
> 90
mmHg
CI > 2
-1
-2
l.min .m
ESC Guidelines. Eur Heart J 2005, 26,384-416
Prehospital Hypotension
and Outcome in Trauma
Arbabi et al J Trauma 2004 , 56 1029
70
Mortality
60
• Register of Ann
Arbor Seattle
USA
• 19 409 patients
• 2373
hypotension
Blunt
50
Penetrating
40
30
20
10
0
120 +
120-90
90-60
60-0
SAP
Prehospital Hypotension = Predictive Factor of Mortality in Trauma
Uncontrolled Hemorrhage :
Is Normal Blood Pressure the Target ?
Roberts et al Lancet 2001
Bleeding
or
Re-bleeding
Mechanic effect
on vascular clot
SAP
Increase
Agressive
Volume
Loading
Hemodilution
Anemia
Hypothermia
Hypoxemia
Coagulation
disorders
Normal blood pressure is not the target !
Is Normalisation of blood Pressure
Dangerous ?????
• Fluid resuscitation interferes with
the physiological response to
hemorrhage
• Elevated blood pressure favors
bleeding by a mechanical effect
• Hemodilution aggavates bleeding
Bickell et al NEJM 1994
The effect of vigorous fluid resuscitation in uncontrolled
hemorrhagic shock after massive splenic injury
Solomonov E , Krausz M
CRIT CARE MED 2000;28:749-754
Uncontrolled Hemorrhage in Rats
MAP
Survival
No fluids
No fluids
LVNS
LVNS
After FR ( LVNS ) : Fall of BP , increase in blood losses and
mortality
Should We Raise Blood Pressure in Case
of Uncontrolled Hemorrhage ?????
Kwan I, Bunn F, Roberts I; WHO Pre-Hospital Trauma Care Steering Committee
Cochrane group 2003.
• Meta-analysis of clinical randomized studies
– 3 studies on survival
– 2 studies on coagulation
• Maximal heterogeneity
Timing and volume of fluid
administration for patients with bleeding
Kwan I, Bunn F, Roberts I; WHO Pre-Hospital Trauma Care Steering Committee
Cochrane group 2003.
found no evidence from randomised
controlled trials for or against early or larger
volume of intravenous fluid administration in
uncontrolled haemorrhage. There is continuing
uncertainty about the best fluid administration
strategy in bleeding trauma patients. Further
randomised controlled trials are needed to
establish the most effective fluid resuscitation
strategy »
1.
« We
Should We Raise Blood Pressure in Case
of Uncontrolled Hemorrhage ?????
Kwan I, Bunn F, Roberts I; WHO Pre-Hospital Trauma Care Steering Committee
Cochrane group 2003.
• Meta-analysis of clinical randomized studies
– 3 studies on survival
– 2 studies on coagulation
• Maximal heterogeneity
==>
No conclusion !!!!!
==>
Experimental data
Uncontrolled hemorrhage and fluid
resuscitation with HSS+HEA or LR in Rats
Burris et Col
J Trauma 1999
REBLEEDING
Permissive
hypotension
rather than the
type of fluid
reduces re
bleeding
Fluid Resuscitation
Permissive Hypotension and Hemorrhagic Shock
Mortality (%) and level of MAP
100%
50%
0%
40 mmHg
1
602mmHg
80
3 mmHg
Stern et al Ann Emerg Med 1993
Fluid Resuscitation
Permissive Hypotension and Hemorrhagic Shock
Burris et al J Trauma 1999; 46 : 216-23
Aortotomy (rat)
MAP
80 mmHg
Su rvival
(%)
80
70
60
50
40
30
20
10
0
MAP
40 mmHg
MAP
100 mmHg
NONE
1
2
3
4
Improved Outcome with Hypotensive Resuscitation ?
Uncontrolled Hemorrhagic shock in a Swine Model
Kowalenko T , et Al J. Trauma , 33 , 349 , 1992
%
Survival
100
•• •• •• •• • •
• •• •
MAP = 40 mmHg
MAP = 80 mmHg
NO RESUSCITATION
Time ( min )
24 immature swines - Aortotomy - Saline Infusion
Normotensive or hypotensive
resuscitation ?
A meta analysis
• 9 randomized studies
• Improvement
• Pooled Risk ratio : 0.37
(0.27 - 0.52)
Mapstone J, Roberts I, Evans PH , J TRAUMA 2003, 55 , 571
Favour hypotensive
Favour normotensive
Permissive hypotension improve survival !
Immediate Versus Delayed Fluid
Resuscitation for Hypotensive Patients
with Penetrating Torso Injuries
Bickell WH, Wall MJ, N. Engl. J. Med. 1994 , 331, 1105 - 9
. 598 patients with torso or cervical injury
. SAP ≤ 90 mmHg at the scene
. No fluid
survival
70 %
. Fluid at the scene
survival
62 % *
p < 0.04
(level I)
Must We Perform Vascular Loading in Multiple Trauma Patients ?
Hemorrhagic shock (rat)
Capone et al J Am Coll Surg 1995; 180 : 49-5
A = « prehospital » period (1 hour)
B = « hospital period (72 h)
60
Group 1 : 0 VL
50
Group 2 : A = No VL ; B =
VL for MAP = 80 mmHg
40
3-D
Survival 30
(%)
20
Group 3 : A = VL for MAP =
40 mmHg ; B MAP = 80
mmHg
10
0
1
2
3
4
Group 4 : A = VL for MAP =
80 mmHg ; B = MAP=80
mmHg
Hypotensive Resuscitation during Active
Hemorrhage: Impact on In-Hospital Mortality
Dutton R, Mackenzie CF , et Al J trauma 2002 , 52, 1141
• Clinical study at Trauma Centrer arrival
• SBP ≤ 90 mmHg and uncontrolled hemorrhage
• Randomisation:
• SBP 100 (n = 55)
SBP 70 (n = 55)
• Survival 92.7 % in each group
Penetrating Trauma and
Hemorrhagic Shock
A military Point of View
• Fluid for
– Radial pulse
• SBP # 80 mmHg
– If impossible, carotide pulse
• SBP # 60 mmHg
• Or keep the patients conscious !!!!
American Armed Forces Medical Services
Combat Fluids Conference July 2001
Permissive Hypotension for
Uncontrollde Hemorrhage
• Strong clinical arguments
• Less clinical evidences
• Indirect arguments
– SBP : 70-90 mmhg
Hypotension and Prognosis in Head Trauma
Patients
The role of secondary brain injury in determining outcome
from severe head injury
Chesnut et al J Trauma 1993, 34 : 216-22
Prospective study in 717 severe brain trauma
patients
SBP < 90 mmHg
MORTALITY x 3
(level III)
Fluid resuscitation of patients with multiple injuries
and severe closed head injury
Experience with an aggressive fluid resuscitation strategy
York et al J Trauma 2000; 48 : 376-80
• 34 patients ISS> 16
•CGS < 8
•PPC > 80 mmHg,
74 % of patients with no cerebral sequellae
6 % mortality
Hemorrhagic Shock
Goals for Blood Pressure
• SBP : 70-90 mmHg if no head trauma
(modulate according to age and underlying disease)
. MAP : 40 mmHg until bleeding is
controlled and then 80 mmHg
• SBP : 120 mmHg in case of head
and / or medullar trauma
How High Should M(S)AP Be ?
Septic shock
MAP : 65 mmHg
1 controlled study
(30 patients)
1 open study (10
patients)
Cardiogenic shock
SAP : > 90-100mmHg
expert opinion
Hemorrhagic shock
SBP : 70-90 mmHg
MAP : 40 mmHg
in case of TBI : SBP 120 mmHg
expert opinion
THE
END
Vasoconstrictor Effets in Hemorrhagic Shock
From De La Coussaye
Vasoconstrictors
Venous bed
Arterial bed
Edema ?
Increased blood
pressure
Increased venous return
with less volume loading
Increased preload
Prehospital volume loading and vasoconstrictors for
severe trauma
SBP < 90mmHg
Penetrating injury
Target: SBP = 70 90
+
Stop volume loading
Volume loading
Crystalloids
Colloids < 20
ml/kg
SBP unstable
or target non
reached
Vasoconstrictor
Blunt trauma
+ TBI GCS < 8
Target: SBP = 120, Ht =
30%
+
Stop volume loading
First priority
surgical hemostasis
Transport and direct
admission to trauma
center
From Carli P, 2005
Hemorrhagic Shock
Hypovolemia
Hemorrhage
Surgery
Vascular loading ?
Transfusion ?
Vasoplegia
Vasopressors ?
Myocardial
Depression
Inotropic
support ?
Meta- analysis of Fluid Challenge on
Survival in Rat Tail resection
Section ≤
50%
Favour fluids
Favour NO fluids
2.88 (1.72 -1.80)
Section ≥
50%
0.25 (0.15 - 0.42)
0.86 (0.63 -1.18)
Roberts I et Al, BMJ 2002 324, 474
Animal models and Uncontrollded Hemorrhage
Literature Analysis
Mapstone J, Roberts I, Evans PH , J TRAUMA 2003, 55 , 571
Large Heterogeneity: Stratification by Model and Severity
44 experimental studies
Model
Aortotomy
Organ Injury
Massive
Hemorrhage:
Fluid
resuscitation
improves the
mortality rate
Adjusted
Risk Ratio
0.48
< 0.001
(0.33 - 0.71)
0.76
0.229
(0.49 - 1.18)
Tail resection
0.69
> 50 %
(0.38 1.25)
Tail resection
1.86
< 50 %
(1.13 - 3.07)
Other vascular
Injury
p
0.221
0.015
1.70
(1.01 2.85)
0.046
Moderate
Hemorrhage :
Fluid
resuscitation
worsens the
mortality rate
FAUT IL CORRIGER LA PRESSION ARTERIELLE A LA
PHASE AIGUE DU CHOC HEMORRAGIQUE ??
Occult hypoperfusion is associated with increased morbidity in
patients undergoing early femur fixation
Crowl et al J Trauma 2000, 48 : 260-7
• 57 Adultes avec fracture(s) fémorale(s) nécessitant
ostéosynthèse
Groupe 1 : 20 patients avec lactate < 2,5
Groupe 2 : 37 patients avec lactate > 2,5 (hypoperfusion
occulte)
Score de gravité identique
• Complications post opératoires :
Groupe 1 : 20 %
Groupe 2 : 50 %
Norepinephrine and Renal Flow
(Endotoxemic
Dogs)
*
*
*
PA
(mmHg)
*
Qr/ml/min
cont NE endo Endo
+ NE
cont NE endo Endo
+ NE
*
CO
cont
NE endo Endo
+ NE
*
RVR
(dynes)
*
cont NE endo Endo
+ NE
Bellomo et al AJRCCM, 1999, 159, 1186-1192
Cardiogenic Shock :
Management of Hypotension
Use Norepinephrine to raise
SBP > 80 mmHg
Change to dopamine
(5-15 mcg/kg/min)
Dobutamine may be given when
SBP > 90 mmHg
ACC/AHA Guidelines 2004
Norepinephrine and Regional Blood
Flow in the Normal Mammalian
Circulation
UF
(ml/h)
Cr CL
ml/min
491+360
90+12 (p<0.05 )
61+18
91+17
Placebo NE
(p<0.05 )
Placebo NE
Giantomasso ICM 2004
Norepinephrine and Regional Blood
Flow in the Normal Mammalian
Circulation
MAP
(mmHg)
4.78 (p<0.05)
104 (p< 0.05)
CO
L/min
3.76
84
Placebo
NE
Placebo
NE
Merino ewes
Placebo or NE : 0.4 g/kg/min
Giantomasso ICM 2004