Fisiologia degli scambi gassosi durante circolazione ... giorno.pdf · Fisiologia degli scambi...

Fisiologia degli scambi

gassosi durante circolazione

extracorporea

2009, Milano

Luciano Gattinoni, MD, FRCP

Università di Milano

Fondazione IRCCS- “Ospedale Maggiore

Policlinico, Mangiagalli, Regina Elena”

Milan, Italy

Oxygenation assessment:

the basicsthe basics

Oxygenation

• Tension

• Content• Content

• Assessment

The basic Physiology

Partial pressure (Tension)

Activity of the unbounded O2molecules

In arterial blood PaO2In venous blood PvO2In alveoli PAO2

PAO2 = FIO2 * 713 – PACO2/RQ

Oxygenation

• Tension


• Assessment

Ox

yg

en S

atu

rati

on

(%

)

92

94

96

98

100

102

54 pts

PaO2 (mmHg)

0 50 100 150 200 250 300

Ox

yg

en S

atu

rati

on

(%

)

80

82

84

86

88

90

r2 = 0.8973

p < 0.0001

54 pts

Maximal binding capacity of hemoglobin

1 mole Hb (64500 gr/M)

4 moles of oxygen (4 x 22.414 L at 0°C and 760 mmHg)

binds

4 moles of oxygen (4 x 22.414 L at 0°C and 760 mmHg)

Therefore

89656 mL/64500 gr = 1.39 mLO2/grHb


Content

total amount of bounded and unbounded O2 molecules

In arterial bloodIn arterial blood

CaO2 = PaO2 x 0.003 + 1.39 x Hb x SataO2

In venous blood

CvO2 = PvO2 x 0.003 + 1.39 x Hb x SatvO2

In lung capillaries (Hp Sat=100%)

CcO2 = PAO2 x 0.003 + 1.39 x Hb x 1

Oxygen Transport (DO2)

DO2 = CaO2 x Qt

normally

1000 mL/L = 200 mL/Lx 5 L1000 mL/L = 200 mL/Lx 5 L

VO2 ≈ 1/4 - 1/5 of DO2

Venous O2 saturation ≈ 0.75 = 1- VO2/DO2

Oxygenation

• Tension


• Assessment

– PaO2/FiO2

– Right to left shunt

– Oxygenation Index (OI)

Anatomical shunt compartment

Gasless tissue

CvO2 CaO2

CvO2

VCO2CcO2

Right to Left Shunt

(CcO2 – CaO2)

(CcO2 – CvO2)

CaO2 x Qt = CcO2 x (Qt-Qs)+CvO2 x Qs

Shunt =

Oxygenation Index = (FIO2 * Mean Airway Pressure) / PaO2

Oxygenation Index

Oxygenation index and severity of lung dysfunction

2–7 Normal or mild pulmonary dysfunction2–7 Normal or mild pulmonary dysfunction

8–9 Moderate pulmonary dysfunction

≥ 10 Severe pulmonary dysfunction

≥ 30 Need for ECMO

Fiser et al. J Heart Lung Transplant 2001;20:631–636.

Oxy

gen

atio

n I

ndex

40

45

50

55

PaO2 60 mmHg

PaO2 50 mmHg

MAP 25 cmH2O

As an example…

67

6071

63

56

50

Oxygen fraction (%)

50 60 70 80 90 100 110

Oxy

gen

atio

n I

ndex

20

25

30

35

100

86

75

67

83

71

P/F ratio

Carbon dioxide assessment:

the basicsthe basics

Carbon dioxide

• Tension


• Assessment


Partial pressure (tension)

Activity of the unbounded CO2molecules

In arterial blood PaCO2In venous blood PvCO2

In alveoli PACO2 ETCO2

Carbon dioxide

• Tension


• Assessment

Contents

Total CO2 = sCO2 + HCO3- + CO3= + PrNHCOO- + NaCO3-

Simplifying

Total CO = 0.03 x PaCO + HCO3-Total CO2 = 0.03 x PaCO2 + HCO3-

i.e.

Total CO2 = 0.03 x PaCO2 x (1 + 10pH-pK)

Remember

1 mMol/L = 2.24 mL%

40

60

80

BE 0

BE -5

BE -10

BE -15

BE -20

con

ten

t(m

L%

)

20 40 60 80 100 120

20

CO

2co

nte

nt

PCO2 (mmHg)

Carbon dioxide

• Tension


• Assessment

Dead Space derivation

VA*PACO2 = VCO2

(VA+VDalv)*PETCO2 = VCO2

(VA+VDalv+VDanat)*PECO2 = VCO2

Alveolar PCO2 = Arterial PCO2

It is assumed that:

Physiological Dead

Space

(PaCO2 – PECO2)

PaCO2

Alveolar Dead Space

(PaCO2 – PETCO2)

PaCO2

Shunt effect

PvCO2 PaCO2

VCO2PcCO2

PcCO2=PACO2

PvCO2

Greater the shunt, greater the difference between

alveolar and arterial CO2

PCO2cascade

PACO2

Ventilated/

perfused lung

Alveolar

VD/VT

PETCO2

Anatomic

VD/VT

PECO2

PvCO2 PaCO2

PvCO2

VCO2PcCO2

perfused lung VD/VT VD/VT

Artificial Lung

• Determinants of oxygenation

• Determinants of Decarboxylation• Determinants of Decarboxylation

• The performance of the membrane

lung

The oxygen charged by the

artificial lung depends,

for a given input saturation, for a given input saturation,

on the blood flow in the

device

Performance

Oxygenator

Input:

37°C

Hb 15 gr/dLHb 15 gr/dL

Sat IN 70%

Bovine blood

Remember that:

The output blood is fully oxygenated,

even at low extracorporeal gas flow

Oxygen transfer is greater with lowerOxygen transfer is greater with lower

input saturation

Oxygen transfer increases linearly with

extracorporeal blood flow

Artificial Lung

• Determinants of oxygenation

• Determinants of Decarboxylation• Determinants of Decarboxylation

• The performance of the membrane

lung

In the venous blood the CO2

content is ≈ 45-50 mL%.

Theoretically from 0.5 L of

blood it is possible to clear the

metabolic CO2 production

Carbon dioxide transfer as a function of blood input pCO2, at different blood flow rates

Kolobow et al Trans. Am. Soc. Artif. Intern. Organs. 1977. 23: 17-21

Performance

Oxygenator

Input:

37°C

Bovine blood

PCO2 45 mmHg

Artificial Lung Performances(11 pts)

Day 1 Day 10

Blood Flow 1 L 2 L

Gas Flow 1.5 L 2.5 L

Input PO2 47 ± 12 mmHg 31 ± 10 mmHgInput PO2 47 ± 12 mmHg 31 ± 10 mmHg

Output PO2 530 ± 80 mmHg 479 ± 80 mmHg

Input PCO2 52.8 ± 8 mmHg 47.7 ± 8 mmHg

Output PCO2 35.4 ± 7 mmHg 29.0 ± 7 mmHg

∆PCO2 17.4 mmHg 18.7 mmHg

Input SatO2 76 ± 8 57 ± 7

CO2 clearance increases with:

Gas flow (primarily)

The logarithm of Blood Flow

Input PCO2

While in natural lung…While in natural lung…

15

20

60

80

100

% DP40 ∆∆∆∆P5

Content/Tension relationship

49

54

( mL/100mL whole blood)

∆∆∆∆C5∆∆∆∆C5

0

5

10

0 20 40 60 80 100 120 140

0

20

40

60%

(mmHg)PO2

DP40 ∆∆∆∆P5

PCO2

35 40 45 503034

39

44

40 40 4580

OXYGENATION

FiO2 =1.0 250 mL min-1

CO REMOVAL

VO2

250

mL min-1

Sata 98%

PaO2 110 mmHgHb 15 g

Satv 82%

PvO2 47 mmHg

7000 mL min-1

PBF

CO2 REMOVAL

VA 9500 mL min-1

VCO2

200

mL min-1

CO2 cont 34 mL

PaCO2 15 mmHg

PvO2 47 mmHg

CO2 cont 52 mL

PvCO2 43 mmHg

1100 mL min-1

PBF

Gattinoni et al., European Advances in Intensive Care, 1983; 21: 97-117

5000

6000

7000

8000

9000

1 104

60

70

80

90

100

110

120

VE

PaCO2V

E (

mL

*min

-1)

Pa

CO

2 (mm

Hg

)

gas flow 10 l/min EC onset

0

1000

2000

3000

4000

5000

0

10

20

30

40

50

60

0 6 12 18 24 30 36 42 48 54 60 66 72

VE

(m

L*m

in (m

mH

g)

Time (h)

Oxygen transfer in artificial and natural lung:

Interaction

The model

Limits of oxygenation in V-V bypass

Consequences of loss of hypoxic

vasoconstriction

Lu

ng

End-capillary blood

Intrapulmonary

shunt

Art

eria

lblo

od

Mixed-venousNatural Lung

Post

lung

O2 natural lung

O2 ECMO

Art

ific

ial

Lu

ng

Pre

lung

Art

eria

l

Body Tissues

VO2

Time course to

equilibrium

Shunt 40%

Art

eri

al O

xyg

en

Sa

tura

tio

n (

%)

94

96

98

100

Mix

ed

Ve

no

us O

xyg

en

Sa

tura

tio

n (

%)

90

95

100QECMO/Qtot 70% QECMO/Qtot 70%

Arterial Oxygen Saturation (%) Mixed Venous Oxygen Saturation (%)

Shunt 40%

STEP

1 2 3 4 5 6 7

Art

eri

al O

xyg

en

Sa

tura

tio

n (

%)

80

82

84

86

88

90

92

94

STEP

1 2 3 4 5 6 7

Mix

ed

Ve

no

us O

xyg

en

Sa

tura

tio

n (

%)

60

65

70

75

80

85

QECMO/Qtot 10%

QECMO/Qtot 10%

Time course to

equilibrium

Shunt 60%

Art

eri

al O

xyg

en

Sa

tura

tio

n (

%)

92

94

96

98

Mix

ed

Ve

no

us O

xyg

en

Sa

tura

tio

n (

%)

85

90

95QECMO/Qtot 70% QECMO/Qtot 70%

Arterial Oxygen Saturation (%) Mixed Venous Oxygen Saturation (%)

STEP

1 2 3 4 5 6 7

Art

eri

al O

xyg

en

Sa

tura

tio

n (

%)

76

78

80

82

84

86

88

90

92

STEP

1 2 3 4 5 6 7

Mix

ed

Ve

no

us O

xyg

en

Sa

tura

tio

n (

%)

60

65

70

75

80

85

QECMO/Qtot 10% QECMO/Qtot 10%

Shunt 60%

The equilibrium is reached when O2

from artificial lung plus O2 from

natural lung equals O2 consumed by2

tissues

VO2 = O2ECMO + O2NATURAL LUNG

Art

eria

l O

xyg

en S

atu

rati

on

(%

)

88

90

92

94

96

(mL

/min

)

340

360

380

400

420

ECMO

mathematical model

Shunt 50%

ECMO blood flow 50%

CO 9 L/min

Hb 11 gr/dL

VO2 250 mL/min

STEP

1 2 3 4 5 6 7

Art

eria

l O

xyg

en S

atu

rati

on

(%

)

78

80

82

84

86

88

VO

2 (

mL

/min

)

240

260

280

300

320

340

O2

tran

sfer


Interaction

The model



vasoconstriction

Steady stateA

rter

ial

Ox

yg

en S

atu

rati

on

(%

)

90

95

100

ECMO

mathematical model

ECMO Blood Flow (%CO)

10 20 30 40 50 60 70

Art

eria

l O

xyg

en S

atu

rati

on

(%

)

75

80

85

90

Shunt 60%

Shunt 50%

Shunt 40%


Interaction

The model



vasoconstriction


Gasless tissue

Fu

ncti

on

al

sh

un

t

0.4

0.6

0.8

1.0

Fu

ncti

on

al

sh

un

t

0.4

0.6

0.8

1.0


0.0 0.2 0.4 0.6 0.8 1.0

Fu

ncti

on

al

sh

un

t

0.0

0.2

0.4


0.0 0.2 0.4 0.6 0.8 1.0

Fu

ncti

on

al

sh

un

t

0.0

0.2

0.4

A B

Cressoni M. et al. Crit Care Med. 2008 Mar;36(3):669-75.

200

300

400

200

300

400

PaO

2/F

IO2

(mm

Hg

)

PaO

2/F

IO2

(mm

Hg

)Anatomical shunt compartment

0.0 0.2 0.4 0.6 0.8 1.0

0

100


0.0 0.2 0.4 0.6 0.8 1.0

0

100

A B

PaO

PaO


Hypoxic vasoconstriction

maintains oxygenation at

different degrees of

anatomical shunt

QS

QT

=Gr. non aerated tissue

Lung Total Weight (gr.)K x

=Perfusion/ gr. non aerated tissue

K

Perfusion Ratio

=Perfusion/ gr. Tot.

K

Assumptions: 1) Edema near homogeneously distributed

2) Qs perfuses only the non aerated tissueHU > -100

HU > -300


Perfusion ratio

and its change

depend on

(R2 0.83)

1) Size of the “bad” lung

2) Global perfusion

3) Hypoxic stimulus

(PsO2 = PvO20.38 x PAO2

0.42)

Perfusion Ratio

(PsO2 = PvO2 x PAO2 )

Decreasing the size

(recruitment)

Decreasing the CO

Perfusion ratio ↑

Perfusion ratio ↓

AS AVERAGE – It does not change

PV

R M

AX

(%

)

60

80

100

Hypoxic vasoconstriction

Theoretical modelPsO2 = PvO2

0.38 x PAO20.42

PVR max (%) = 100 x (PsO2-2.616)/(6.683 x 10-5 + PsO2

-2.61)

PvO2

0 20 40 60 80 100

PV

R M

AX

(%

)

0

20

40

FiO2 40%FiO2 60%FiO2 80%FiO2 100%

Therefore don’t be surprised

if providing 3-4 L ECMO

fully oxygenated blood flow,

arterial PaO2 and saturationarterial PaO2 and saturation

change minimally, since

functional shunt tends to

increase

Decarboxylation: interaction with

spontaneous and mechanical breathing

Control of breathing using an

extracorporeal membrane lung

The lung rest concept

Kolobow T, Gattinoni et al., Anesthesiology, 1977; 46: 138-141

This happens also in

spontaneously breathing menspontaneously breathing men

during CO2 removal

Alveolar ventilation as a function of CO2 elimination

Gattinoni et al Anest. e Rianim. 1977. 18(4): 396-406

Gattinoni et al Anest. e Rianim. 1977. 18(4): 396-406

Control of intermittent positive pressure breathing

(IPPB) by extracorporeal removal of carbon dioxide

Gattinoni et al., Br. J. Anesth., 1978; 50: 753

Corso Teorico-Pratico

Trattamento

dell’Insufficienza Respiratoria Acuta

mediante Supporto Extracorporeo

Centro di Simulazione

Fondazione IRCCS Policlinico, Mangiagalli e Regina Elena

Milano

2009

Il circuito extracorporeo:

Tipologie possibili

Giorgio IottiAnestesia e Rianimazione 2

Pavia

Sistema Respiratorio

Pump Failure

Lung Failure

Scambiatore di Gas

Pompa

Insp

Esp

INSUFFICIENZA RESPIRATORIA

PUMP FAILURE - IPERCAPNICA

Inquadramento Diagnostico Fisiopatologico


PUMP FAILURE - IPERCAPNICA LUNG FAILURE - IPOSSIEMICA

Inquadramento Diagnostico Fisiopatologico

• The syndrome did not respond to usual and ordinary methods of respiratory and ordinary methods of respiratory therapy

• The syndrome did not respond to usual and ordinary methods of respiratory and ordinary methods of respiratory therapy

• Positive end-expiratory pressure (PEEP) was most helpful in combating atelectasys and hypoxemia

CPT

Vtidal

FRC

VolumiPolmonari

StartStart

Plim

Ptidal

EEP

PressioniAlveolari

CPT

Vtidal

FRC

VolumiPolmonari

↓ VtStart ↓ VtStart

Plim

Ptidal

EEP

PressioniAlveolari

CPT

Vtidal

FRC

VolumiPolmonari

↓ VtStart ↑ Freq.↓ VtStart

Plim

Ptidal

EEP

PressioniAlveolari

↑ Freq.



• Ossigeno• Ventilazione protettiva• Ventilazione protettiva• ↓ spazio morto• Pronazione• Manovre di reclutamento• iNO• Attività resp. spontanea

UTILIZZO OTTIMALE / MASSIMALE

DELL’ORGANO MALATO

Il gioco qualche volta non funziona…

• Anche con tutti i trucchi, le acrobazie e le precauzioni che abbiamo imparato, talvolta la sola POMPA ARTIFICIALEtalvolta la sola POMPA ARTIFICIALEnon basta:

– Severa IPERCAPNIA

–Pericolosa IPOSSIEMIA



• Ossigeno• Ventilazione protettiva• Ventilazione protettiva• ↓ spazio morto• Pronazione• Manovre di reclutamento• iNO• Attività resp. spontanea

UTILIZZO OTTIMALE / MASSIMALE

DELL’ORGANO MALATOSOSTITUZIONE con

ORGANO ARTIFICIALE

Supporto Respiratorio Extracorporeo

• Prelevo del sangue

• Lo tratto con uno scambiatore di gas Extra Corporeo a MembranaExtra Corporeo a Membrana

� Rimozione di CO2 (CO2R) ECCO2R

� + Ossigenazione (O) ECMO

• Reinfondo il sangue trattato

va ECMO

Rimozione di CO2

Ossigenazione

Assist. Cardiaca

JAMA 1979; 242:2193-6

Extracorporeal membrane oxygenation in severe acute respiratory

failure. A randomized prospective study.

Zapol WM, Snider MT, Hill JD, Fallat RJ, Bartlett RH, Edmunds LH,

Morris AH, Peirce EC 2nd, Thomas AN, Proctor HJ, Drinker PA, Pratt

PC, Bagniewski A, Miller RG Jr.

Nine medical centers collaborated in a prospective randomized study to

evaluate prolonged extracorporeal membrane oxygenation (ECMO) as a

therapy for severe acute respiratory failure (ARF). Ninety adult patients were therapy for severe acute respiratory failure (ARF). Ninety adult patients were

selected by common criteria of arterial hypoxemia and treated with either

conventional mechanical ventilation (48 patients) or mechanical ventilation

supplemented with partial venoarterial bypass (42 patients). Four patients in

each group survived. The majority of patients suffered acute bacterial or viral

pneumonia (57%). All nine patients with pulmonary embolism and six

patients with posttraumatic acute respiratory failure died. The majority of

patients died of progressive reduction of transpulmonary gas exchange and

decreased compliance due to diffuse pulmonary inflammation, necrosis, and

fibrosis. We conclude that ECMO can support respiratory gas exchange but

did not increase the probability of long-term survival in patients with severe

ARF.

vv ECMO

Rimozione di CO2

Ossigenazione

Kolobow T, Zapol W, Pierce J (1969) Trans Am Soc Artif Intern Organs 15:172-7

Anesth Analg 57: 470: 1978

av ECLA

(ILA Novalung)

Rimozione di CO2

A confronto

va ECMO

Rimozione di CO2

Ossigenazione

Assist. Cardiaca

vaECMO respiratoria: problemi

• Fortissima dipendenza dal supporto extracorporeo

• Ridotta perfusione polmonare• Ridotta perfusione polmonare

• Scarsa ossigenazione del sangue in uscita da VS (coronarie, tronchi sovraortici)

• Problemi di perfusione distale della zona dipendente dall’arteria incannulata

• Embolizzazione sistemica

av ECLA

(ILA Novalung)

Rimozione di CO2

avECLA: vantaggi

• Bassa richiesta di tecnologia

– Semplicità

– Investimenti ridotti

– Facile trasportabilità– Facile trasportabilità

• Comunque necessari:

– Misuratore flusso extracorporea

– Flussimetro di precisione

– Hemochron (ACT)

avECLA: problemi

• Notevole aumento della richiesta di prestazione cardiaca (shunt a-v)

• Dipendenza dalle condizioni emodinamiche del paziente

• Ridotta perfusione distale della zona dipendente dall’arteria incannulatadall’arteria incannulata

• Dispersione di calore (scambiatore di calore assente)

• Facilità di passaggio di gas nella camera ematica dell’ossigenatore (pressione transmembrana!!)

• Facilità di apposizioni trombotiche dell’ossigenatore (flusso relativamente basso)

• Scarsa capacità di ossigenazione

avECLA: problemi

• Scarsa capacità di ossigenazione

• Se bisogna passare allo step successivo (vvECMO), abbiamo fatto un grosso buco in un’arteria!

vv ECMO

Rimozione di CO2

Ossigenazione

vvECMO: limiti

• Capacità di ossigenazione: non consente un supporto totale

• Assistenza cardiaca: nessuna, se non • Assistenza cardiaca: nessuna, se non indiretta

Decapnizzatori

• vvECMO a bassissimo flusso

• Nessuna ossigenazione

• CO2 removal molto limitato• CO2 removal molto limitato

• Circuiteria da CRRT

– non eparinata

– Pompa sangue ?

– Concepita per uso discontinuo

– Cambi, tempo e impegno, costi

Conclusioni

• A voi le conclusioni sulla “ECMO respiratoria” più appropriata oggirespiratoria” più appropriata oggi

La gestione del ventilatore ed

interazione con il bypass

Giuseppe Foti

Istituto Anestesia e RianimazioneIstituto Anestesia e Rianimazione

Università di Milano-Bicocca

dir. Prof. A. Pesenti

Ospedale S. Gerardo Monza

…….ma adesso che sono in bypass,

il ventilatore

serve ancora ?

VENTILAZIONE OSSIGENAZIONE

Cosa succede alla partenza della

CEC

Rimozione > 70% VCO2Rimozione > 70% VCO2

PCO2 !!

ATTENZIONE SHIFT pH e

PCO2 !!

• � subito

– FR (sempre)

– TV (se necessario)– TV (se necessario)

– I/E (attenzione)

• Guided by:

– EndTidalCO2

– EGA

• entro 10’

Se non serve più ventilare, perché

tengo il ventilatore ?

• Malgrado �ECBF la PaO2 può essere �

• ECBF/C.O.

• � SvO2 � �Vasocostrizione ipossica

PO2 e PAP

PAPPAP

�� Flusso CECFlusso CEC�� SvOSvO22

SvOSvO22

Se non serve più ventilare, perché

tengo il ventilatore ?

• Per Ossigenare

Come

• Tenendo aperto il polmone

FR = 30

Paw = [(30*1) + (15*1)] / 2 = 22.5

30

Attenzione ai cambi bruschi di

Pmedia

FR = 15

Paw = [(30*1) + (15*2)] / 3 = 20

30

1” 1”

15

30

1” 2”

15

30


Pmedia


Pmedia

• Evitare immediatamente la sovradistensione

• Ridurre Pplat < 30

• TV < 6 ml/Kg

NO GOOD BETTER

Perché/Come contrastare i bruschi

cambi Pmedia ?

Perché/Come contrastare i bruschi

cambi Pmedia ?

• Dereclutamento

(Plasmorrea/Capillary Leak)

• �� PEEP

• Evitando �� I/E

Strategie Ventilatorie in ECMO

(una guerra di religione)

Recruiter Non Recruiter

High survival in adult patients with ARDS treated by High survival in adult patients with ARDS treated by extracorporeal membrane oxygenation, extracorporeal membrane oxygenation, minimal minimal sedation, and pressure supported ventilationsedation, and pressure supported ventilation

Linden V et al. Linden V et al. ICM 2000; 26: 1630ICM 2000; 26: 1630

�� 17 patients17 patients

�� LIS 3.5LIS 3.5�� LIS 3.5LIS 3.5

�� PaOPaO22/FiO/FiO22 46 mmHg46 mmHg

�� Length of bypass 3Length of bypass 3--52 days52 days

��((conventionalconventional VV or VA 9/17)VV or VA 9/17)

�� PEEP 10 PSV 15PEEP 10 PSV 15

�� Survival Rate 76 %Survival Rate 76 %

lung rest settings were :

- peak inspiratory pressure 20–25,

- positive endexpiratory pressure 10–15,

- rate 10,

- FiO2 0・3.

Recruiter strategy

� PAW

� B.F.

Non Recruiter strategy

� PAW

� B.F.


• Low PEEP (5-10)

• LPS

– PSV

• High Blood Flow• High Blood Flow

– II° drainage cannula

• NO PNX

•• PulmonaryPulmonary HypertensionHypertension

–– VV--A bypass?A bypass?

� B.F.

Reclutamento e PAP

PAP

PVCPVC

RMs = 70 cmH2ORMs = 70 cmH2O


In 33 patients (49%), a secondaccesscannula was needed to augmentcannula was needed to augmentECMO support.

Recruiter strategy

• RMs

• PEEP Titration

• SIGH

•• PNX ?PNX ?•• PNX ?PNX ?

%

Opening and closing pressures

30

40

50

Opening

pressure

Closing

pressure

Paw > 35 cmH2O

to fully recruit

Paw [cmH2O]

0 5 10 15 20 25 30 35 40 45 500

10

20 pressure

Crotti et al. Am J Respir Crit Care Med 2001

Modern PEEP TitrationModern PEEP Titration

10 1215

7

10

Spo2 e RM’s

• � � Problema risolto !Era un’atelettasia

• � e poi � � Ripeto e � PEEP

•± �� Pressione Rm’s

oppure aspetto

Quante RM’s ?

• Pochissime se uso SIGH

• In Controllata e Assistita

• Che pressione ? � quella di reclutamento• Che pressione ? � quella di reclutamento

• A chi ? � A quelli che reclutano

Sigh (1 ogni 3 min)

Effects of periodic lung recruitment maneuvers on gas exchange and

respiratory mechanics in mechanically ventilated ARDS patients.G. Foti, M.Cereda, M.E. Sparacino, L. De Marchi,F. Villa, A. Pesenti Intensive Care Med (2000) 26: 501-507

Pressione di reclutamento

Sigh (1 ogni 3 min)

↑Oxygenation

↓↓↓↓ Qva/Qt

SIGH

Monitoraggio

reclutamento

Monitoraggio

reclutamento• EGA

– P/F

– PaO2 al 100%

– Shunt– Shunt

– Rapporto B.F./C.O.

• Meccanica respiratoria

– Cpl, FRC

• Imaging

– Rx

– TC

Monitoraggio reclutamento

durante V-A bypass

• Quale sangue proviene dai polmoni ?

• Incannula la radiale dx• Incannula la radiale dx

– Se attività cardiaca

– Sangue proveniente dal polmone naturale

Oh..oh…c’è un PNX

• Presto mettiamo drenaggio toracico

• Aspettiamo e convertiamoci

Oh..oh…c’è un PNX

• Non mi convertirò mai!

– Dg percutaneo

– Guidato scopia– Guidato scopia

– Identificazione eco

• Bene, non sbolla più

• Tiriamolo via

•• Non rimuovete le frecce Non rimuovete le frecce

durante CEC (durante CEC (…augh…augh))

Identificazione Ecografica PNX

Sono passate ormai 2

settimane…dobbiamo fare la tracheo.

• Se proprio non se ne può fare a meno

• Percutanea meglio che chirurgica

• Fantoni meglio delle altre

– Attenzione al tracheoscopio rigido– Attenzione al tracheoscopio rigido

– Tecnica con fibroscopia flessibile

– Mantenete Paw con il tubino

– Sospendere/ridurre eparina

When a ALI/ARDS pts. can be When a ALI/ARDS pts. can be

weaned to PSV from CMV ?weaned to PSV from CMV ?

n.s.181±67218±68PaO2/FiO2

pFailureFailure22%

SuccessSuccess78%

PaO2 > 80

PEEP < 15

< .0520.2 ±19.29.2 ±13.5Days from

Tube

< .050.70 ±0.090.52 ±0.10Vd/Vt

< .0530 ±1642 ± 15Cst,rs

(ml/cmH2O)

Cereda M, Foti G. et al. Crit Care Med 2000 Vol.28 n° 5; 1269-1275

BENEFICI Respiro Spontaneo in ARDS

spontaneous breathing controlled ventilation, NMBA

Set: BIPAP+PSV, Pmax = 35-40cmH2O

Ti = 3-5 s.

RRBIPAP = 0.5-1 b.p.m.

ECMO per favorire il passaggio

al respiro assistito

• Quando è terminata fase iperacuta

– No capillary leak

• Per favorire reclutamento alveolare• Per favorire reclutamento alveolare

• Per accelerare il weaning

• Dottore..dottore..la frequenza respiratoria �– Aumenta PSV..mmm..no anzi

– Sedalo un pochino…..mmm….,aspetta

– Aumenta gas flow !

E se facessimo a meno del ventilatore ?del ventilatore ?

2/87 Survival

in Intubated in Intubated

because of Pneumonia

Ventilazione Diversamente

Invasiva (DIV)

1 Week

CEC

P/F 64

PEEP 15

GB 280

Plt 19.000

P/F 104

PEEP 10

GB 1050

Plt 33.000

Start

CEC

Pediatric ECMO Management: Pulmonary

• Optimal ventilator settings vary

• Limit peak pressures to 30 cm H2OH2O

• Delivered tidal volumes 4-6 cc/kg

• Rate 5-10 breaths/minute

• PEEP 12-15 cm H2O

• Inspiratory time longer

• Goal FiO2 0.21

Federico Pappalardo, MD

Department of Cardiothoracic and Vascular Anesthesia and Intensive Care

Università Vita e Salute San Raffaele Hospital, Milano

� Hemorrhagic complications 54% (37/68)

• ECMO cannulation site 22%

• GI bleeding 10%

• Respiratory tract 10%• Respiratory tract 10%

• Intracranial hemorrhage 9%

• Genital bleeding 9%

� Median amount of blood administered per patient 1880 mL

� NO thromboembolic complications ???

Overall adult ECLS SurvivalOverall adult ECLS Survival

Respiratory 53%

Cardiac 32%

ELSO Registry (100 centers)

Cardiac 32%

eCPR 37%

THROMBIN GENERATION/EFFECTS

XaXVIIIa, , PLCa++

Tissue Factor(TF:VIIa)

*

IXa

IX

Contact(XIIa)

Prothrombin

PT fragment 1.2

Va, Ca++

THROMBIN

, PL

FPAXIII

FV, FVIII, FXI FXIa, FVa/FVIIIa

Platelets

BTG, PF4

activation/consumption

*TFPI

bradykinin

APC

FVi, FVIIIi

Thrombomodulin*

Protein C

ATIII

ATIII

ATIII

ATIII

*

PT fragment 1.2

Fibrin (M)Fibrinogen

Fibrin (Ps)

Fibrin (Pi)

XIIIa

tPA*

EC

Plasminogen PLASMIN

D-dimer

FSP

Platelet GP1bPAP complexes

-2-antiplasmin

PAI1

tPA:PAI1*

TAT

ATIII

Injury of vessels wallleads to contact between blood and subendothelial cells

Tissue factor (TF) isexposed and binds toFVIIa or FVII whichis subsequently converted to FVIIa

1. Initiation phase

FXa binds to FVa on thecell surface

The complex between TF and FVIIa activates FIX and FX

The FXa/FVa complexconverts small amountsof prothrombin intothrombin

The small amount ofthrombin generatedactivates FVIII, FV, FXIand platelets locally.FXIa converts FIX to FIXa

2. Amplification phase

Activated plateletsbind FVa, FVIIIaand FIXa

The FVIIIa/FIXa complexactivates FX on thesurfaces of activatedplatelets

FXa in association withFVa converts largeamounts of prothrombininto thrombin creating a “thrombin burst”.

3. Propagation phase

The “thrombin burst”leads to the formationof a stable fibrin clot.

ASA, Dipyridamol, Clopidogrel

Heparin

Coumadin

PAT

aPTT

INR

TEG

• Haemostasis starts with the interaction between TF

and FVIIa on the surface of subendothelial cells.

• The small amount of thrombin generated during the amplification phase activates platelets locally on whose surface the subsequent reactions take place.whose surface the subsequent reactions take place.

• The resulting thrombin burst results in the formation of a stable clot.

Activation Balance

Inappropriate

Site

Inappropriate

Amount

Inappropriate Control

ThrombosisDVT/PTE

MIStroke

Bleeding

Transfusion

Inappropriate Control

� Contact activation : interface of blood with nonendothelial surface

� Pericardial activation : mediated by trasfusion of pericardial bloodpericardial blood

� Mechanical consumption : shear forces imposed by circuit’s component

� Pulsatile, axial or centrifugal device

� Cannulation (apical, atrial)

� Coagulation disease (anti-phospholipid antibodies,..)

� Heart disease (acute infarction, icmp, myocarditis,

Anticoagulation ManagementAnticoagulation Management

� Heart disease (acute infarction, icmp, myocarditis,

dcmp)

� Cardiac rhythm (fibrillation)

� Age (children)

Anticoagulation management

safe

Anticoagulation ManagementAnticoagulation Management

Anticoagulation management

low costs simple

Heparin activates platelets directly-GP IIb/IIIa activated-P-selectin expressed

+ Platelet Activated

Platelet

HeparinP-selectin

GP IIb/IIIa

Low concentrations of heparin increase the affinity of thrombin for fibrin.

Fibrin

ThrombinThrombin

ThrombinHeparin

+Thrombin

Heparin can induce

Heparin inactivated by Platelet Factor 4 (PF4)

FibrinHeparin can induce an immune response in the form of HIT/HITTS and lead to thrombocytopenia and thrombosis

Anti-bodies

Platelet

Factor 4+Heparin

Fibrin

2

1

Thrombin2

1

Thrombin

2

1

ThrombinHeparin

Heparin cannot bind clot-bound thrombin

P P

P

P

P

Heparin binds to plasma proteins and cells

PP

Cell

PPCell

PP

Heparin exhibitsa nonlinear

dose-response.

Heparin dose

AC

T

�UFH continues to dominate ECMO anticoagulation:

• rapidly acting

• easily reversible

• inexpensive

• widely available

• well tollerated by pediatrics and adults

• needs cofactor AT, produce inhibition of factor Xa, thrombin and TF • needs cofactor AT, produce inhibition of factor Xa, thrombin and TF

• thrombin bound to clot or surface of the circuit is not inhibited by AT-UFH complex

Bound thrombin activate clotting and thrombin generation

GREATER UFH NEEDS

4000

5000 D-Dimer ( ng / ml )

Increased Heparin to

Preserve Haemostasis• High Heparin had

reduced:

– Prothrombin activation

� β−Thromboglobulin

Despotis et al Thromb Hemostasis 1996;76:902-8

2000

3000

Control High Hep

� The effectiveness of anticoagulation worsens with the duration of ECMO (6 days freedom from thromboembolic events)

� Management of ECMO anticoagulation partially derived from the experiences of CPB

� The popular range for the ACT with UFH during ECMO is 180 to

220 sec220 sec

� aPTT is a valuable tool to assess anticoagulation in situation that do not require high heparin dosing such as ECMO

� In very ill patients requiring continuous infusion of UFH the ACT can not delineate between low and moderate level of anticoagulation compared with aPTT

Dosage of Acetylsalicylacide

Low dosage:Thromboxane A2 (platelet)-> reduction of aggregation

High dosage:Prostacyclin (endothelium)

Dosage of Acetylsalicylacide

Prostacyclin (endothelium)-> increasing aggregation

High dosage:Prostaglandin (stomac)

-> increasing GI-bleeding

0

50

100

150

200

250

300

350

400

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

400

500

600

Platelets and shockPlatelets and shock

0

100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

0

100

200

300

400

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Grafic 1.: LVAD and RHF

Grafic 2.: LVAD survival

Grafic 3.: TAH survival

Platelets and shockPlatelets and shock

“Platelet transfusion represents a major part of

management of ECMO patients”

“Recurrent platelet dysfunction on ECMO”

“Frequent platelets transfusions even with

normal platelet count” normal platelet count”

“The more critically ill the patient, the more likely

platelets have been given”

LABORATORY TESTING

• Antigen assays- ELISA detects antibodies

reactive against the PF4/Heparin complex

- High sensitivity (90-98%)- High negative predictive

value

• Activation/Functional assays

- SRA (Serotonin release assay)

- Platelet aggregation assay

- Detect the presence of antibodies that activate platelets in the presence of heparin

- High sensitivity (>95%)

- High negative predictive valuevalue

- Moderate positive predictive value

- The magnitude of a positive ELISA can be diagnostically useful

- High negative predictive value

- Moderate positive predictive value

- The magnitude of a positive ELISA can be diagnostically useful

The presence of HIT antibodies does not necessarily predict the development of clinical HIT!!

There is no single laboratory test that perfectly correlates

with a clinical diagnosis of HIT, because there is currently no

test with 100% sensitivity and specificity for the detection of

pathogenic HIT antibodies

LABORATORY TESTING

pathogenic HIT antibodies

Do

STOP heparin

Switch to alternate anticoagulantSwitch to alternate anticoagulant

Don’t Do

No warfarin (Vit K if warfarin given)

No prophylactic platelets

Dx

HIT antibodies

Ultrasound for lower-limb DVT

COO-

+H3N

Lepirudin Bivalirudin Argatroban

+H3N

BIVALENT DTI UNIVALENT DTI

DTIDTI

Lepirudin Bivalirudin Argatroban

RENAL ENZIMATIC>RENAL HEPATICElimination

Binding

Effect on INR

Immunogenicity

REVERSIBLE REVERSIBLEIRREVERSIBLE

+ ++ ++++

+++ + -

�Reversible binding to thrombin - BIVALENT DTI�Blocks activation by thrombin of fibrinogen, Fact. V,VIII,XIII and platelets�Cleaved by circulating proteases� Half-life 25-30’

Bivalirudin Bivalirudin

� Half-life 25-30’� Proteolytic clevage by thrombin (80%)� Removal by haemofiltration� AVOID STASIS

Set upSet up

� Albumin in priming

� Consider UF in presence of lung injury and/or capillary leak syndrome

� Heparin bolus 1000 UI after cannulation, then check for bleeding

If bleeding <50 cc/h � start heparin infusion to a target

ACT 180-200, aPTT 60 sec

If bleeding on heparin > 50 ml/h � stopIf bleeding on heparin > 50 ml/h � stop

� 2 UI/mL of heparin in the priming� Weaning ACT >200

ECMO circuit changeECMO circuit change

� Plasma leak

� Hemolysis likely if:

• Pressure > 300 mmHg on arterial cannula

• Negative pressure > 200 on the venous cannula

• LDH>1000 mg/dL and FHb >40 mg/dL in two samples within 24h• LDH>1000 mg/dL and FHb >40 mg/dL in two samples within 24h

� Thrombi Check HIT

� Thrombocytopenia

� Sistematically every 8-10 days

WeaningWeaning

� Always keep 0.5L flow (risk of thrombosis)

� If flow is stopped for definitive evaluation

(30 min. observation)

give heparin 10000 UI before lines clamping

� Recirculation

Figure 1.: RVAD Impeller after 33 days of support Figure 2.: RVAD Impeller after 3 days of low flow support

Fisiologia degli scambi gassosi durante circolazione ... giorno.pdf · Fisiologia degli scambi...

Documents

Transcript of Fisiologia degli scambi gassosi durante circolazione ... giorno.pdf · Fisiologia degli scambi...