How Hight Should MAP Be

1
How Hight Should MAP Be ?

• C Martin MD,FCCM,FCCP
• ICU and Trauma Center
• Nord University Marseilles France

2
150 100 50 0
Autoregulation in Health and Disease
Organ Blood Flow ( baseline)
Autoregulatory threshold

• Below their autoregulatory thresholds, organ
  flows are linearly dependent on perfusion
  pressure.

Subautoregulatory slope
20 40 60 80 100 Organ
Artery Pressure (mmHg)
3
What about settings where organ autoregulation
is lost ?
4
150 100 50 0
Autoregulation in Disease
Organ Blood Flow ( baseline)
Control 3 weeks 1 week
20 40 60 80 100 Organ
Artery Pressure (mmH g)
5
Any increase in organ perfusion is likely to
augment organ blood flow
6
150 100 50 0
Autoregulation in Disease
Organ Blood Flow ( baseline)
Control 3 weeks 1 week
20 40 60 80 100 Ogan
Artery Pressure (mmH g)
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Norepinephrine and Regional Blood
Flow during Hyperdynamic Sepsis

• Merino ewes IV bolus of E. coli (3x109)
• Norepinephrine 0.4 ?g/kg/min or placebo

8 0.8 (plt0.05 )
CO L/min
877 (p lt 0.05)
MAP (mmHg)
7.212
698
Placebo
NE
Placebo
NE
Giantomasso ICM 2004
9
Norepinephrine and Regional Blood
Flow during Hyperdynamic Sepsis
CrCL mlL/min
UF (ml/h)
83 54 (plt0.05 )
117101 p lt 0.05)
4130
5223
Placebo
NE
Placebo
NE
Giantomasso ICM 2004
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What is the relevance of these
experimentalstudies to clinical practice???
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Norepinephrine and Renal Blood Flow
MAPressure
Urine Flow ml/h
Time
Time
Hesselvik CCM 1989 Martin CCM 1990 Martin Chest
1994 .
Desjars CCM 1983, 1987 Meadows CCM 1988
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Norepinephrine in Septic and Non-Septic Patients

Septic shock
Creatinine
1.70.9 p lt 0.05
Cr CL
300137
180110 p lt 0.05
0.7 0.3
before
24hr
before
24hr
Creatinine
Cr CL
Head trauma
2.7 0.6
2.80.7
10717
10027
24hr
24hr
before
before
Albanese et al Chest 2004,126,534-539
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MAP 65-75-85 mmHg ???
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150 100 50 0
Autoregulation in Disease
Organl Blood Flow ( baseline)
Control 3 weeks 1 week
20 40 60 80 100 Organ
Artery Pressure (mmH g)
16
150 100 50 0
Autoregulation in Disease
Organ Blood Flow ( baseline)
Control 3 weeks 1 week
20 40 60 80 100 Organ
Artery Pressure (mmH g)
17
150 100 50 0
Autoregulation in Disease
Organ Blood Flow ( baseline)
Control 3 weeks 1 week
20 40 60 80 100 Organ
Artery Pressure (mmH g)
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Increasing MAP ?
10 septic shock patients treated by NE
CI

DO2
VO2

• LeDoux et al Crit Care Med
• 2000 , 28 , 2729

19

• Increasing MAP ?

• 10 septic shock patients treated by NE

UF

• LeDoux et al Crit Care Med
• 2000 , 28 , 2729

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65
85
21
A Bourgoin et al CCM 2005,33,780-786
Lactate
Increasing MAP ?
65
85
DO2
VO2
22
UF
Increasing MAP ?
65
85
Creatinine
Cr Cl
A Bourgoin et al CCM 2005,33,780-786
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MAP 65 mmHg
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Unresolved issues Formerly hypertensive
patients ?Elderly patients ?Atherosclerotic
patients ?Others ????
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Coronary Artery flow
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Cardiogenic ShockManagement of Hypotension
SBP gt 90 mmHg
CI gt 2 l.min-1.m-2
ESC Guidelines. Eur Heart J 2005, 26,384-416
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Prehospital Hypotension and Outcome in Trauma
Arbabi et al J Trauma 2004 , 56 1029
Mortality

• Register of Ann Arbor Seattle USA
• 19 409 patients
• 2373 hypotension

SAP
Prehospital Hypotension Predictive Factor of
Mortality in Trauma
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Uncontrolled Hemorrhage Is Normal Blood
Pressure the Target ?
Roberts et al Lancet 2001
Agressive Volume Loading
Bleeding or Re-bleeding
SAP Increase
Mechanic effect on vascular clot
Hemodilution
Anemia Hypothermia Hypoxemia
Coagulation disorders
Normal blood pressure is not the target !
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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
36
The effect of vigorous fluid resuscitation in
uncontrolled hemorrhagic shock after massive
splenic injury

• Solomonov E , Krausz M CRIT CARE MED
  200028749-754
• Uncontrolled Hemorrhage in Rats

Survival

• After FR ( LVNS ) Fall of BP , increase in
  blood losses and mortality

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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

38
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.

•  We 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 

39
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
• gt No conclusion !!!!!
• gt Experimental data

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Uncontrolled hemorrhage and fluid resuscitation
with HSSHEA or LR in Rats
Burris et Col J Trauma 1999
REBLEEDING
Permissive hypotension rather than the type of
fluid reduces re bleeding
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Fluid Resuscitation Permissive Hypotension and
Hemorrhagic Shock
40 mmHg 60 mmHg 80 mmHg
Stern et al Ann Emerg Med 1993
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Fluid Resuscitation Permissive Hypotension and
Hemorrhagic Shock
Burris et al J Trauma 1999 46
216-23 Aortotomy (rat)
MAP 80 mmHg
MAP 40 mmHg
MAP 100 mmHg
NONE
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Improved Outcome with Hypotensive Resuscitation
? Uncontrolled Hemorrhagic shock in a Swine
Model
Kowalenko T , et Al J. Trauma , 33 , 349 , 1992










100
Survival




MAP 40 mmHg
MAP 80 mmHg
NO RESUSCITATION
Time ( min )
24 immature swines - Aortotomy - Saline Infusion
44
Normotensive or hypotensiveresuscitation ?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
Permissive hypotension improve survival !
45
Immediate Versus Delayed FluidResuscitation for
Hypotensive Patientswith 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 lt 0.04
(level I)
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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)
Group 1 0 VL Group 2 A No VL B VL
for MAP 80 mmHg Group 3 A VL for MAP
40 mmHg  B MAP 80 mmHg Group 4 A VL for
MAP 80 mmHg  B MAP80 mmHg
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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

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Penetrating Trauma andHemorrhagic ShockA
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
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Permissive Hypotension for Uncontrollde Hemorrhage

• Strong clinical arguments
• Less clinical evidences
• Indirect arguments
• SBP 70-90 mmhg

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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 lt 90 mmHg
• MORTALITY x 3

(level III)
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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 ISSgt 16
• CGS lt 8
• PPC gt 80 mmHg,

74 of patients with no cerebral sequellae 6
mortality
52

53

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Hemorrhagic ShockGoals 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

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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 gt 90-100mmHg expert
opinion
Hemorrhagic shock SBP 70-90 mmHg MAP 40
mmHg in case of TBI SBP 120 mmHg expert
opinion
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THE END
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Vasoconstrictor Effets in Hemorrhagic Shock
From De La Coussaye
Vasoconstrictors
Venous bed
Arterial bed
Edema ?
Increased venous return with less volume loading
Increased blood pressure
Increased preload
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Prehospital volume loading and vasoconstrictors
for severe trauma
SBP lt 90mmHg
Blunt trauma TBI GCS lt 8 Target SBP 120,
Ht 30
Volume loading Crystalloids Colloids lt 20 ml/kg
Penetrating injury Target SBP 70 90
-
-
SBP unstable or target non reached


Stop volume loading
Stop volume loading
Vasoconstrictor
First priority surgical hemostasis
Transport and direct admission to trauma center
From Carli P, 2005
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Hemorrhagic Shock
Hypovolemia Hemorrhage
Vasoplegia
Myocardial Depression
Surgery Vascular loading ? Transfusion ?
Vasopressors ?
Inotropic support ?
60
Meta- analysis of Fluid Challenge onSurvival in
Rat Tail resection
Section 50
Section 50
Roberts I et Al, BMJ 2002 324, 474
61
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
Moderate Hemorrhage Fluid resuscitation
worsens the mortality rate
Massive Hemorrhage Fluid resuscitation improves
the mortality rate
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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 lt 2,5
• Groupe 2 37 patients avec lactate gt 2,5
  (hypoperfusion occulte)
• Score de gravité identique
• Complications post opératoires
• Groupe 1 20
• Groupe 2 50

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Norepinephrine and Renal Flow(Endotoxemic Dogs)




PA (mmHg)
Qr/ml/min
cont
NE
endo
Endo NE
cont
NE
endo
Endo NE



RVR (dynes)
CO
cont
NE
endo
Endo NE
cont
NE
endo
Endo NE
Bellomo et al AJRCCM, 1999, 159, 1186-1192
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Cardiogenic Shock Management of Hypotension
Use Norepinephrine to raise SBP gt 80 mmHg
Change to dopamine (5-15 mcg/kg/min)
Dobutamine may be given when SBP gt 90 mmHg
ACC/AHA Guidelines 2004
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Norepinephrine and Regional Blood
Flow in the Normal Mammalian Circulation
UF (ml/h)
Cr CL ml/min
9012 (plt0.05 )
491360
6118
9117
(plt0.05 )
NE
Placebo
NE
Placebo
Giantomasso ICM 2004
69
Norepinephrine and Regional Blood
Flow in the Normal Mammalian Circulation
4.78 (plt0.05)
MAP (mmHg)
CO L/min
104
(plt 0.05)
3.76
84
Placebo
NE
Placebo
NE

• Merino ewes
• Placebo or NE 0.4 ?g/kg/min

Giantomasso ICM 2004