how hight should map be ? c martin md,fccm,fccp icu and trauma center nord university marseilles...

How Hight Should MAP

Be ?C Martin MD,FCCM,FCCP

ICU and Trauma Center

Nord University Marseilles France

20 40 60 80 100

Organ Artery Pressure (mmHg)

Organ Blood Flow (% baseline)

150

100

50

0

Subautoregulatory slope

Autoregulatorythreshold

Autoregulationin Health and Disease

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

What about settings

where organ

autoregulation is

lost ?

20 40 60 80 100

Organ Artery Pressure (mmH g)

Organ Blood Flow (% baseline)

150

100

50

0

Autoregulationin Disease

Control3 weeks

1 week

Any increase in organ

perfusion is likely to

augment

organ blood flow

20 40 60 80 100

Ogan Artery Pressure (mmH g)

Organ Blood Flow (% baseline)

150

100

50

0

Autoregulationin Disease

Control3 weeks

1 week

Norepinephrine and Regional Blood

Giantomasso ICM 2004

MAP(mmHg)

Placebo NE Placebo NE

COL/min

Flow during Hyperdynamic Sepsis

69+8

87+7 (p < 0.05)

7.2+12

8 + 0.8 (p<0.05 )

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

Norepinephrine and Regional Blood

Giantomasso ICM 2004

UF(ml/h)

Placebo NE Placebo NE

CrCLmlL/min

Flow during Hyperdynamic Sepsis

52+23

117+101 p < 0.05)

41+30

83 + 54 (p<0.05 )

What is the relevance of these experimental

studies to clinical practice???

Norepinephrine and Renal Blood Flow

Urine Flow ml/hMAPressure

Desjars CCM 1983, 1987Meadows CCM 1988

Hesselvik CCM 1989Martin CCM 1990Martin Chest 1994……….

Time Time

Norepinephrine in Septic and Non-Septic Patients

Septic shock

Head trauma

Creatinine

Creatinine

before 24hr before 24hr

24hr 24hrbefore before

300+137

180+110 p < 0.050.7 + 0.3

1.7+0.9 p < 0.05

100+27 107+17 2.8+0.7 2.7+ 0.6

Cr CL

Cr CL

Albanese et al Chest 2004,126,534-539

MAP : 65-75-85 mmHg ???

20 40 60 80 100

Organ Artery Pressure (mmH g)

Organl Blood Flow (% baseline)

150

100

50

0

Autoregulationin Disease

Control3 weeks1 week

20 40 60 80 100

Organ Artery Pressure (mmH g)

Organ Blood Flow (% baseline)

150

100

50

0

Autoregulationin Disease

Control3 weeks1 week

20 40 60 80 100

Organ Artery Pressure (mmH g)

Organ Blood Flow (% baseline)

150

100

50

0

Autoregulationin Disease

Control3 weeks1 week

4,2

4,4

4,6

4,8

5

5,2

5,4

5,6

MAP 65 MAP 75 MAP 85

CI

* *

560

580

600

620

640

660

680

700

720

MAP 65 MAP 75 MAP 85

DO2

0

20

40

60

80

100

120

140

160

MAP 65 MA 75 MAP 85

VO2

*

Increasing MAP ?10 septic shock patientstreated by NE

•LeDoux et al Crit Care Med2000 , 28 , 2729

CI

VO2

DO2

0

10

20

30

40

50

60

MAP 65 MAP 75 MAP 85

Urine flow

0

0,05

0,1

0,15

0,2

0,25

0,3

0,35

0,4

0,45

MAP 65 MAP 75 MAP 85

Red cell velocity

0

2

4

6

8

10

12

14

16

18

MAP 65 MAP 75 MAP 85

Pa-PiCo2

•Increasing MAP ?•10 septic shock patients treated by NE

•LeDoux et al Crit Care Med2000 , 28 , 2729

UF

65 85

A Bourgoin et al CCM 2005,33,780-786

Increasing MAP ?Lactate

DO2

VO2

65 85

Increasing MAP ?UF

Creatinine

Cr ClA Bourgoin et al CCM 2005,33,780-786

8565

MAP : 65 mmHg

Unresolved issues :

Formerly hypertensive patients ?Elderly patients ?

Atherosclerotic patients ?Others ????

Coronary Artery flow

Cardiogenic ShockManagement of Hypotension

SBP> 90

mmHg

ESC Guidelines. Eur Heart J 2005, 26,384-416

CI > 2 l.min-

1.m-2

Prehospital Hypotension

and Outcome in Trauma

0

10

20

30

40

50

60

70

120 + 120-90 90-60 60-0

Blunt

Penetrating

Arbabi et al J Trauma 2004 , 56 1029

• Register of Ann Arbor Seattle USA

• 19 409 patients• 2373

hypotension

SAP

Mortality

Prehospital Hypotension = Predictive Factor of Mortality in Trauma

Uncontrolled Hemorrhage :Is Normal Blood Pressure the

Target ?Roberts et al Lancet 2001

Normal blood pressure is not the target !

Bleeding or

Re-bleeding

Hemodilution

Coagulation disorders

Agressive Volume Loading

AnemiaHypothermia Hypoxemia

SAPIncrease Mechanic effect

on vascular clot

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

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

SurvivalMAP

No fluids

LVNS

No fluids

LVNS

Should We Raise Blood Pressure in Case of Uncontrolled Hemorrhage ?????

• Meta-analysis of clinical randomized studies– 3 studies on survival

– 2 studies on coagulation

• Maximal heterogeneity

Kwan I, Bunn F, Roberts I; WHO Pre-Hospital Trauma Care Steering Committee

Cochrane group 2003.

Timing and volume of fluid administration for patients with bleeding

1. « 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 »

Kwan I, Bunn F, Roberts I; WHO Pre-Hospital Trauma Care Steering Committee

Cochrane group 2003.

Should We Raise Blood Pressure in Case of Uncontrolled Hemorrhage ?????

• Meta-analysis of clinical randomized studies– 3 studies on survival

– 2 studies on coagulation

• Maximal heterogeneity

==> No conclusion !!!!!

==> Experimental data

Kwan I, Bunn F, Roberts I; WHO Pre-Hospital Trauma Care Steering Committee

Cochrane group 2003.

Uncontrolled hemorrhage and fluid resuscitation with HSS+HEA or LR in Rats

Burris et Col J Trauma 1999

Permissive

hypotension

rather than the

type of fluid

reduces re

bleeding

REBLEEDING

0%

50%

100%

1 2 3

Mortality (%) and level of MAP

Stern et al Ann Emerg Med 1993

40 mmHg 60 mmHg 80 mmHg

Fluid ResuscitationPermissive Hypotension and Hemorrhagic Shock

Fluid ResuscitationPermissive Hypotension and Hemorrhagic Shock

Fluid ResuscitationPermissive Hypotension and Hemorrhagic Shock

Fluid ResuscitationPermissive Hypotension and Hemorrhagic Shock

Burris et al J Trauma 1999; 46 : 216-23

Aortotomy (rat)

01020304050607080

Survival (%)

1 2 3 4

NONE

MAP 80 mmHg MAP

40 mmHgMAP

100 mmHg

Improved Outcome with Hypotensive Resuscitation ? Uncontrolled Hemorrhagic shock in a Swine Model

Improved Outcome with Hypotensive Resuscitation ? Uncontrolled Hemorrhagic shock in a Swine Model

Kowalenko T , et Al J. Trauma , 33 , 349 , 1992

24 immature swines - Aortotomy - Saline Infusion

%Survival

Time ( min )

•• ••• •• •• • • •

••MAP = 40 mmHg

MAP = 80 mmHg

NO RESUSCITATION

100

Normotensive or hypotensive

resuscitation ?A meta analysis

• 9 randomized studies

• Improvement

• Pooled Risk ratio : 0.37 (0.27 - 0.52)

Permissive hypotension improve survival !

Mapstone J, Roberts I, Evans PH , J TRAUMA 2003, 55 , 571

Favour hypotensive Favour normotensive

Immediate Versus Delayed FluidResuscitation for Hypotensive Patients

with Penetrating Torso Injuries

Immediate Versus Delayed FluidResuscitation for Hypotensive Patients

with Penetrating Torso Injuries

. 598 patients with torso or cervical injury

. SAP ≤ 90 mmHg at the scene

. No fluid survival 70 %

. Fluid at the scene survival 62 % *

Bickell WH, Wall MJ, N. Engl. J. Med. 1994 , 331, 1105 - 9

p < 0.04(level I)

Hemorrhagic shock (rat)

Capone et al J Am Coll Surg 1995; 180 : 49-5A = « 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 = MAP=80 mmHg

0

10

20

30

40

50

60

3-DSurvival

(%)

1 2 3 4

Must We Perform Vascular Loading in Multiple Trauma Patients ?

Hypotensive Resuscitation during Active Hemorrhage: Impact on In-Hospital Mortality

• 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

Dutton R, Mackenzie CF , et Al J trauma 2002 , 52, 1141

Penetrating Trauma and

Hemorrhagic Shock

A military Point of View

American Armed Forces Medical ServicesCombat Fluids Conference July 2001

• Fluid for

– Radial pulse

• SBP 80 mmHg

– If impossible, carotide pulse

• SBP # 60 mmHg

• Or keep the patients conscious !!!!

Permissive Hypotension for Uncontrollde Hemorrhage

• Strong clinical arguments

• Less clinical evidences

• Indirect arguments– SBP : 70-90 mmhg

SBP < 90 mmHg

MORTALITY x 3(level III)

Hypotension and Prognosis in Head Trauma Patients

The role of secondary brain injury in determining outcome from severe head injuryChesnut et al J Trauma 1993, 34 : 216-22

Prospective study in 717 severe brain trauma patients

Fluid resuscitation of patients with multiple injuries

and severe closed head injury

Experience with an aggressive fluid resuscitation strategy

• 34 patients ISS> 16

•CGS < 8

•PPC > 80 mmHg,

York et al J Trauma 2000; 48 : 376-80

74 % of patients with no cerebral sequellae

6 % mortality

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

How High Should M(S)AP Be ?

Septic shock MAP : 65 mmHg1 controlled study (30 patients)1 open study (10 patients)

Cardiogenic shock SAP : > 90-100mmHg expert opinion

Hemorrhagic shockSBP : 70-90 mmHgMAP : 40 mmHgin case of TBI : SBP 120 mmHg expert opinion

THE END

Vasoconstrictors

Arterial bed

Increased venous returnwith less volume loading

Increased preload Increased blood

pressure

Edema ?

Venous bed

Vasoconstrictor Effets in Hemorrhagic Shock Vasoconstrictor Effets in Hemorrhagic Shock

From De La Coussaye

Prehospital volume loading and vasoconstrictors for Prehospital volume loading and vasoconstrictors for severe traumasevere trauma

Prehospital volume loading and vasoconstrictors for Prehospital volume loading and vasoconstrictors for severe traumasevere trauma

SBP < 90mmHgSBP < 90mmHg

Volume loadingVolume loading

Crystalloids Crystalloids

Colloids < 20 Colloids < 20 ml/kgml/kg

Transport and direct Transport and direct admission to trauma admission to trauma

centercenter

++

First priorityFirst priority

surgical hemostasissurgical hemostasis

--

StopStop volume loadingvolume loading VasoconstrictorVasoconstrictor StopStop volume loadingvolume loading

--++

SBP unstable SBP unstable

or target non or target non reachedreached

From Carli P, 2005

Blunt trauma

+ TBI GCS < 8

Target: SBP = 120, Ht = 30%

Penetrating injury

Target: SBP = 70 90

HypovolemiaHemorrhage Vasoplegia Myocardial

Depression

SurgeryVascular loading ?Transfusion ?

Vasopressors ? Inotropic support ?

Hemorrhagic Shock

Meta- analysis of Fluid Challenge onSurvival in Rat Tail resection

Favour fluids Favour NO fluids

2.88 (1.72 -1.80)

0.25 (0.15 - 0.42)

0.86 (0.63 -1.18)

Section ≤ 50%

Section ≥ 50%

Roberts I et Al, BMJ 2002 324, 474

Animal models and Uncontrollded Hemorrhage Literature Analysis

Large Heterogeneity: Stratification by Model and Severity

Mapstone J, Roberts I, Evans PH , J TRAUMA 2003, 55 , 571

ModelAdjusted

Risk Ratio p

Aortotomy0.48

(0.33 - 0.71)< 0.001

Organ Injury0.76

(0.49 - 1.18)0.229

Tail resection

> 50 %0.69

(0.38 - 1.25)0.221

Tail resection

< 50 %1.86

(1.13 - 3.07)0.015

Other vascular

Injury1.70

(1.01 - 2.85)0.046

44 experimental studies

Massive Hemorrhage:

Fluid resuscitation improves the mortality rate

Massive Hemorrhage:

Fluid resuscitation improves the mortality rate

Moderate Hemorrhage :

Fluid resuscitation worsens the mortality rate

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)

Bellomo et al AJRCCM, 1999, 159, 1186-1192

PA (mmHg)

CORVR

(dynes)

Qr/ml/min

cont NE endoEndo+ NE

cont NE endoEndo+ NE

*

cont NE endoEndo+ NE

*

cont NEendoEndo+ NE

**

* *

*

Cardiogenic Shock :Management of Hypotension

Use Norepinephrine to raiseSBP > 80 mmHg

Change to dopamine (5-15 mcg/kg/min)

ACC/AHA Guidelines 2004

Dobutamine may be given when SBP > 90 mmHg

Norepinephrine and Regional Blood

Giantomasso ICM 2004

UF(ml/h)

Placebo NE Placebo NE

Cr CLml/min

Flow in the Normal MammalianCirculation

91+17

491+360

61+18

90+12 (p<0.05 )

(p<0.05 )

Norepinephrine and Regional Blood

Merino ewesPlacebo or NE : 0.4 g/kg/min

Giantomasso ICM 2004

MAP(mmHg)

Placebo NEPlacebo NE

COL/min

Flow in the Normal Mammalian Circulation

84

104 (p< 0.05) 3.76

4.78 (p<0.05)