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
FACTORS GOVERNING PaO2 & PaCO2
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
FACTORS GOVERNING PaO2 & PaCO2
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)
BL 15 min 30 min POST
NIMV
700
600
500
400
300
200
* *
VT (
ml)
BL 15 min 30 min POST
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
BL 15 min 30 min POST
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
BL 15 min 30 min POST
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%
Baseline 30 min 90 min
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
COPD Exacerbation & Convalescence:Salbutamol Response
Polverino E et al. AJRCCM 2007;176:350-5
Baseline 30 min 90 min
Car
diac
Out
put
(L/m
in)
5
6
7
8*
*
ACUTE
STABLE
COPD Exacerbation & Convalescence:Salbutamol Response
+12%
**+23%
Polverino E et al. AJRCCM 2007;176:350-5
Baseline 30 min 90 min
200
220
240
260
O2 U
ptak
e (m
L/m
in)
ACUTE
STABLE
COPD Exacerbation & Convalescence:Salbutamol Response
*
+10%
Polverino E et al. AJRCCM 2007;176:350-5
Baseline 30 min 90 min
PaO
2 (m
m H
g)
55
60
65
70
75
80ACUTE
STABLE
COPD Exacerbation & Convalescence:Salbutamol Response
Polverino E et al. AJRCCM 2007;176:350-5
p<0.01
**
p<0.05
-7.5 mmHg
Baseline 30 min 90 min
PaC
O2
(mm
Hg)
38
40
42
44
46
48ACUTE
STABLE
COPD Exacerbation & Convalescence:Salbutamol Response
Polverino E et al. AJRCCM 2007;176:350-5
Baseline 30 min 90 min
VA/Q
Mis
mat
ch (
DIS
P R
-E*)
10
12
14
16
18
20ACUTE
STABLE
..
COPD Exacerbation & Convalescence:Salbutamol Response
Polverino E et al. AJRCCM 2007;176:350-5
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