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ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni
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ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

Mar 31, 2015

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Page 1: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

ABCABCAdvanced Bleeding

Care

Goals of Resuscitation:Early Versus Late Targets

Luciano Gattinoni

Page 2: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

© TPWG May 2004

ABCABCAdvanced Bleeding

Care

2

Energy Charge

Energy charge

Rel

ativ

e sp

eed

0 0.25 0.5 0.75 1

ATP synthesis

ATP consumption

Page 3: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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During Glycolysis

For 1 mole of glucose, only 2 moles of ATP produced (efficiency = 5%)

No O2 is consumed and no CO2 is produced

No H+ is released into the medium

Lactate formation is essential for NADH re-oxidation

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© TPWG May 2004

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Matrix

Inter-membrane space

NADH + H+ NAD+

4H+

Q

QH2

succinate fumarate

Q

QH2

2H+2Cyt c

2H+

4H+

4H+

2H+

½O2 H2O

COMPLEX I COMPLEX II COMPLEX III COMPLEX IV

Inn

er

Glycolysis

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© TPWG May 2004

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Matrix

3H+

3H+

ADP + Pi

ATP

Inter-membrane space

Inn

er

mem

bra

ne

H+ H+H+ H+

H+

ATP SYNTHASE

ATP Synthesis

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To Maintain Energy Charge

ATP synthesis sufficient to compensate for- Mechanical work- Active transport (ions and molecules)- Synthesis of biomolecules

Mitochondria must be structurally and functionally intact

Page 7: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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Fresh water turtle Hibernating frog

Oxyconformers

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Metabolic shut-down

Protein synthesis , half-life

Channel arrest ( ion-motive ATPases)

Decreased electron transport and proton leaks

90 – 95% decrease in demand

Oxyconformers

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© TPWG May 2004

ABCABCAdvanced Bleeding

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Cat Man

Oxyregulators

Page 10: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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Flow redistribution

Partial oxygen conformance (shut-down)

Metabolic rearrangement (Pasteur)

Oxyregulators

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© TPWG May 2004

ABCABCAdvanced Bleeding

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Metabolic shut down(Protein synthesis )

=VO2 / O2 dependency

Secondary mitochondrial damage

Necrosis Apoptosis

Hours

Oxyregulators

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Metabolic Rearrangement

Wenger RH J Exp Biol 2000; 203 Pt 8: 1253

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HFI - 1

Glycolyticenzymes

Krebsenzymes

Gene Regulation

Metabolic Rearrangement

Page 14: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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Mammalian cells respond to energy failure with- Increased glycolysis

- Lactate and acidosis

- Oxygen conformance- Decreased protein synthesis

- Both are short-term mechanisms

Secondary Mitochondrial Dysfunction

ApoptosisNecrosis

Mammalian Cell Response

Page 15: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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Markers for Energy Failure

Oxygen debt concept

Venous oxygen saturation

Lactate and acidosis

Venous / tissue pCO2

Page 16: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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Estimated in ICU as decreased VO2

Time

VO

2 (L

/min

)

Hypothetical baseline

Oxygen Debt

Measured as increased VO2

after muscle exercise

Time

VO

2 (L

/min

)

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A debt of 25 mL O2 / min to be paid by anaerobic ATP production

would imply

0.017 mol ATP / min = 0.017 mol Lactate /min

12.240 mmol Lactate / 24 hours

Oxygen conformance is mandatory !!!

=

Long-Lasting Oxygen Debt?

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Physiological Background

SatvO2 = SataO2 -VO2 (mL/min)

Q (L/min)

1

Hb (g/L) x 1.39x

SatvO2 = metabolism

haemodynamic

1

carrierxLung -

Page 19: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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19N

egat

ive

char

ges

SID Approach

Co

nc

entr

ati

on

(m

Eq

/L)

0

20

40

60

80

100

120

140

160

HCO3-

A-

Po

siti

ve c

har

ges

HCO3-

A-

OH-

SID

SID

BB

BB

DSID = Actual SID – Reference SIDBE = Actual BB – Reference BB

DSID = BE

Neg

ativ

e ch

arg

es

OH-

Page 20: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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Alkalosis Acidosis

Mortality and Acidosis at Entry

721 Critically Ill Patients

< 200 20 - 25

25 - 30

30 - 35

35 - 40

40 - 45

45 - 50

50 - 55

55 - 60

> 60

20

40

60

80

100

H+ [nanomoles/litre]

Mo

rta

lity

dis

trib

utio

n (

%)

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Importance of Mixed Venous pCO2

CO2 content vs. CO2 tension

CvCO2 = CaCO2 + VCO2/Q

CvO2 = CaO2 - VO2/Q

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20 40 60 80 100 120

20

40

60

80

CO

2 c

on

ten

t (

mL

%)

pCO2 (mm Hg)

CO2 Dissociation Curve(Whole Blood)

BE 0BE -5BE -10BE -15BE -20

Each curve is described at constant

Base Excess. As shown, for the same

CO2 content,

changing the Base Excess causes a

great change of pCO2

(see the broken line parallel to axes)

Page 23: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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lemondrops+

Coc

aCol

a

pCO2+

HCO3-

The Coca Cola Effect

Coc

aCol

a

pCO2

HCO3-

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Low SatvO2 may or may not indicate energy failure

All indicate energy failure

• Low pH

• High lactate• Negative BE• Decreased SID• High PvCO2

Indeed…

Page 25: ABC Advanced Bleeding Care Goals of Resuscitation: Early Versus Late Targets Luciano Gattinoni.

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Energy failure

BE - Lactate

Pump failure or mitochondrial dysfunction

Haemodynamic failure

Pump failure

Volume test

VO2 Lactate

Mitochondrial dysfunction

VO2 Lactate

Dobutaminetest

VO2 Lactate

VO2 Lactate

Haemodynamic and Mitochondrial Failure

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Absence of energy failure

Reserve at limit

Goodreserve

Dobutamine test(stress test)

VO2

Lactate=

VO2

Lactate=

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Pro

bab

ilit

y o

f su

rviv

al

Days after randomization0 45 90 135 180

0.00.10.20.30.40.50.60.70.80.91.0

Patients at risk (N° of events)

257 (133) 106 (16) 89 (4) 85 (1) 84

Oxygen-saturation group (164 events)

252 (129) 108 (13) 94 (4) 90 (3) 87

Control group (157 events)

253 (133) 102 (8) 90 (4) 86 (3) 83

Cardiac index group (156 events)

Gattinoni L et al. N Engl J Med 1995; 333: 1025

Survival Curves

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SvO2 70%

Baseline SvO2 Control 49.2

Treated 48.6

Mortality

Early Goal Directed Therapy

Control therapy

n = 133

Treatment

n = 130

P

In hospital 46.5% 30.5% 0.009

28 days 49.2% 33.3% 0.01

60 days 56.9% 44.3% 0.03

Rivers E et al. N Engl J Med 2001; 345: 1368

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Pre-operative ER ICUDay 2 Day 7

ShoemakerChest 1988

DO2 target

C38%

T*21%

C70.7

48.4%

CI72.1

48.6%

SVO2

71.752.1%

GattinoniNEJM 1995

C67.3

CI68.2

SVO2

69.7

RiversNEJM 2001 SVO2

49.2% 48.6%SVO2

65.3% 70.3%C T*

46.5 30.5

Shoemaker WC et al. Chest 1988; 94: 1176;Gattinoni L et al. N Engl J Med 1995; 333: 1025; Rivers E et al. N Engl J Med 2001; 345: 1368

Haemodynamic Treatment in Critically Ill Patients

Time frame

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0-2020-40

40-6060-80

80-100

Mo

rtal

ity

(%)

0

20

40

60

80

100

84 60 88 127 376Patients

Percentage of Time Within 70% SatvO2 Target

Gattinoni L et al. N Engl J Med 1995; 333: 1025

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Conclusion

Energy failure may be due to primitive haemodynamic inadequacy and/or mitochondrial dysfunction

Volume and dobutamine test may help in diagnosis

Prolonged energy failure leads to irreversible mitochondrial dysfunction (necrosis - apoptosis)

Early intervention may prevent irreversible secondary damage