Mar del Plata, 10-13 Octubre 2014 R Rodriguez-Roisin UNIVERSITAT DE BARCELONA Utilidad clínico-terapéutica de la investigación del intercambio gaseoso

Mar del Plata, 10-13 Octubre 2014R Rodriguez-Roisin

UNIVERSITATDE

BARCELONA

Utilidad clínico-terapéuticade la investigación del

intercambio gaseoso en la EPOC

Técnica de eliminación de gases inertes múltiples (MIGET)

Wagner PD et al. JAP 1974;36:588-99

Estima cualitativa y cuantitativamente las distribuciones de flujo sanguíneo pulmonar y de ventilación alveolar (relaciones VA/Q).

Cuantifica el shunt intrapulmonar, el desequilibrio de las relaciones VA/Q y la limitación de la difusión de oxígeno, componentes esenciales de la diferencia alveolo-arterial de oxígeno (AaPO2).

Estima la interacción de los factores pulmonares y no-pulmonares determinantes del intercambio gaseoso.

3

VENTILATION-PERFUSION RATIO

0.001 0.01 0.1 1.0 10 100

VE

NT

ILA

TIO

N (

)

AN

D B

LOO

D F

LOW

(

), L

/min

0.00

0.15

0.30

0.45

0.60

0.75

0.90

DeadSpace

Shunt

VA/Q ratio distributions in normal individuals

Log SDQ

Log SDV

Arterial Hypoxemia:Ventilation-perfusion mismatching Increased intrapulmonary shuntDiffusion limitation to oxygenAlveolar hypoventilation

Arterial Hypercapnia:Alveolar hypoventilation Ventilation-perfusion mismatching

Causes of abnormal PaO2 & PaCO2

Arterial Hypoxemia:Ventilation-perfusion mismatching Increased intrapulmonary shuntDiffusion limitation to oxygenAlveolar hypoventilation

Arterial Hypercapnia:Alveolar hypoventilation Ventilation-perfusion mismatching

Causes of abnormal PaO2 & PaCO2

Factors governing PaO2 & PaCO2

FACTORS GOVERNING PaO2 & PaCO2

VENTILATION-PERFUSIONIMBALANCE

SHUNT

DIFFUSIONLIMITATION

INSPIREDOXYGEN

ALVEOLARVENTILATION

CARDIAC OUTPUT

OXYGENUPTAKE

COPD: structure & function

Alveolar Wall DestructionAir Spaces Enlargement

Alveolar AttachmentsLoss

HIGH VA/Q RATIOS

Capillary Network Reduction

Small AirwaysNarrowing-Distortion

Nonhomogeneous Inspired Air Distribution

LOW VA/Q RATIOS

Reduced Ventilation In Dependent Alveoli

AIRFLOWLIMITATION

GAS TRAPPING-LUNG HYPERINFLATION

Rodríguez-Roisin R & MacNee W. ERM 2006;38:177-200

AIRFLOW LIMITATION

GAS TRAPPING

LUNG HYPERINFLATION

9

0

0.30

0.50

0.70

0.90

1.10

1.30

1.50

Grades

VA/Q mismatching by GOLD grades

1 2 3 4

LO

G S

DQ

&L

OG

SD

V

Rodríguez-Roisin R et al. JAP 2009;106:1902-8

Effects of 100% oxygen breathing in COPD exacerbations

Santos C et al. AJRCCM 2000;161:26-31

Further VA/Q worsening while breathing 100%

oxygen in COPD points to a very active hypoxic

pulmonary vasoconstriction reversion

COPD

COPD

COPD

ARDS

ARDS

ARDS

Mechanisms of VA/Q worsening in COPD exacerbation

Hypoxic vasoconstriction reversion

Airflow limitation Mucus hypersecretion Gas trapping-lung hyperinflation Increased cardiac output

..

Increased oxygen uptake


VENTILATION-PERFUSIONVENTILATION-PERFUSIONIMBALANCEIMBALANCE

SHUNTSHUNT

DIFFUSIONDIFFUSION

LIMITATIONLIMITATION

INSPIREDINSPIREDOXYGENOXYGEN

ALVEOLARALVEOLARVENTILATIONVENTILATION

CARDIAC CARDIAC OUTPUTOUTPUT

OXYGENOXYGENUPTAKEUPTAKE

Effects of 100% oxygen breathing in COPD exacerbations

Santos C et al. AJRCCM 2000;161:26-31

Further VA/Q worsening while breathing 100%

oxygen in COPD points to a very active hypoxic

pulmonary vasoconstriction reversion

COPD

COPD

COPD

ARDS

ARDS

ARDS

Alveolar gas equation for carbon dioxide

=AlveolarVentilation PaCO2

CO2 Production . K


VENTILATION-PERFUSIONVENTILATION-PERFUSIONIMBALANCEIMBALANCE

SHUNTSHUNT

DIFFUSIONDIFFUSIONLIMITATIONLIMITATION

INSPIREDINSPIREDOXYGENOXYGEN

ALVEOLARALVEOLARVENTILATIONVENTILATION

CARDIAC CARDIAC OUTPUTOUTPUT

OXYGENOXYGENUPTAKEUPTAKE

CaO2 -Cardiac Output

Oxygen ConsumptionCvO2 =

CardiacOutput

CaO2 - CvO2

=Oxygen Consumption

Fick Principle

CaO2 -Cardiac Output

Oxygen ConsumptionCvO2 =

CardiacOutput

CaO2 - CvO2

=Oxygen Consumption

Fick principle

I

VA/Q. .

PaO2v

Mixed venous PO2 (mm Hg)

100

90

80

70

60

50

40

30

15 20 25 30 40 4535

Art

eri

al PO

2 (

mm

Hg

)

Mixed venous and arterial PO2 interplay

0.9

1.21.51.8

COPDpatients

0.3 0.6 Healthysubjects

SCENARIO # 1:

Arterial Hypoxemia& COPD

Exacerbations

Ventilation-Perfusion Worsening

46%

COPD Exacerbations: Determinants of

Hypoxemia

Barberà JA et al. ERJ 1997;10:1285-91

Low Mixed Venous PO2

26%

Increased Oxygen Consumption

28%

PaO2

FALL

INCREASEDVO2

DECREASEDMixed Venous

PO2

DECREASEDPaO2

WORSENINGVA/Q

MISMATCH

COPD EXACERBATION

SCENARIO # 2:

NIV & COPD Exacerbations

COPD EXACERBATION AND NIMV ( SD)

BL 15 min 30 min POST

NIMV

35

30

25

20

15

10

**f

(min

-1)


NIMV

700

600

500

400

300

200

* *

VT (

ml)


NIMV

10.0

8.0

6.0

4.0

* *

QT (

L/m

in)

.

Diaz O et al. AJRCCM 1997;156:1840-5

COPD EXACERBATION AND NIMV ( SD)

Diaz O et al. AJRCCM 1997;156:1840-5

80

70

60

50

40


NIMV

PaO

2

PaC

O2

(m

m H

g)

**

*

7.50

7.40

7.30

7.20BL 15 min 30 min POST

NIMV

pH

* *

25

20

15

10


NIMV

VA/Q

MIS

MA

TC

H

.

.

PaO2

COPD Exacerbation & NIV

MINUTEVENTILATION

PaO2 PaO2

CARDIACOUTPUT

PvO2UNCHANGED

VA/QMISMATCH

SCENARIO # 3:

SABAs & COPD Exacerbations

INCREASED QT

(Vasodilatation?)BRONCHODILATION

INCREASEDArterial

PO2

INCREASEDMixed venous

PO2

FINALArterial

PO2

WORSENINGVA/Q

MISMATCH

DECREASEDArterial

PO2

COPD Exacerbation & SABAs

?

Baseline 30 min 90 min

FE

V1

(% P

redi

cted

)

15

25

35

45

55ACUTE

STABLE* *

* *

COPD Exacerbation & Convalescence:Salbutamol Response

Polverino E et al. AJRCCM 2007;176:350-5

+16%

+15%


Min

ute

Ven

tilat

ion

(L/m

in)

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

ACUTE

STABLE

p<0.05




Car

diac

Out

put

(L/m

in)

5

6

7

8*

*

ACUTE

STABLE


+12%

**+23%



200

220

240

260

O2 U

ptak

e (m

L/m

in)

ACUTE

STABLE


*

+10%



PaO

2 (m

m H

g)

55

60

65

70

75

80ACUTE

STABLE



p<0.01

**

p<0.05

-7.5 mmHg


PaC

O2

(mm

Hg)

38

40

42

44

46

48ACUTE

STABLE




VA/Q

Mis

mat

ch (

DIS

P R

-E*)

10

12

14

16

18

20ACUTE

STABLE

..



p<0.05

*

*

+29%

+ 6%

UNCHANGED PaO2

INCREASED QT(Vasodilatation?)

INCREASEDmixed venous

PO2

UNCHANGEDVA/Q

MISMATCH

UNCHANGEDPaO2

Bronchodilation

IncreasedPaO2

COPD: SABAs & Exacerbation

?

InflammatoryMediators

airwaylumen

Inflammatory

Mediators

leaky epithelium

leaky post-capillary venule

Bronchial Circulation

Inflammatory

Mediators

2-agonist

2-receptors

COPD: SABAs & Convalescence

Bronchodilation

IncreasedPaO2

INCREASEDVO2

DECREASEDmixed venous

PO2

PaO2

FALL

DECREASEDPaO2

INCREASED QT

(Vasodilatation?)

INCREASEDmixed venous

PO2

WORSENINGVA/Q

MISMATCH

+ + +

BronchodilatorsGlucocorticoids

AntibioticsOxygentherapy Mechanical

Ventilation

Fluid RestrictionDiureticsInotropics

Gas Exchange & COPD Exacerbation: Therapeutical Implications

VA/QMISMATCH

MINUTEVENTILATION

OXYGENCONSUMPTION

CARDIAC OUTPUT

. .

Rodríguez-Roisin R. Thorax 2006;61:535-44

Documents

Mar del Plata, 10-13 Octubre 2014 R Rodriguez-Roisin UNIVERSITAT DE BARCELONA Utilidad clínico-terapéutica de la investigación del intercambio gaseoso