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Oxygen / ventilatory support in COPD
University Medical Centre Groningen
The Netherlands
OXYGEN
MEDICATION
LTX
Severe COPD
LVRS
VENTILATORY
SUPPORT
REHABILITATION
OXYGEN
MEDICATION
LTX
Severe COPD
LVRS
VENTILATORY
SUPPORT
REHABILITATION
100
203 subjects randomized to continuous or 12
hours of oxygen for at least 12 months
90
NOTT
Cumulative Survival %
80
87 subjects randomized to
oxygen 15 hours/day or none
19 hrs
70
MRC
60
50
15 hrs
12 hrs
40
No Oxygen
30
20
10
0
0
10
20
30
40
50
60
70
80
Time (months)
Composite slide NOTT and MRC studies
Dynamic Hyperinflation in COPD
• Increases work of breathing from added elastic
loads
• Respiratory muscles at a mechanical disadvantage
• Contributes to the sensation of dyspnea with
increasing inspiratory pressures
30
28
26
24
22
20
18
0.2
0.3 0.5 0.75 1.0
FiO2
3
14
Endurance time (min)
32
Inspiratory capacity (L)
Respiratory rate (breath/min)
Effect of Oxygen in 10 Non-hypoxemic
Patients with Severe COPD, During
Constant Work
2.5
2
1.5
1
0.5
0.2
0.3
12
10
8
6
4
2
0.5 0.75 1.0
FiO2
0.2
0.3
0.5
0.75
1.0
FiO2
Modified from Somfay A, ERJ 2001;18:77
Medical Volume Reduction with Oxygen
Reduces ventilation
Reduces air trapping
Reduces hyperinflation
Relieves dyspnea
Increases exercise
Improves health-related quality of life
Systematic Review of RCT’s of Short Term
Benefit of Ambulatory Oxygen in COPD
Exercise capacity – Endurance distance
Oxygen
N
Placebo
N
Davidson 1988
17
17
1.32
52.00 (1.96, 102.04)
Fujimoto 2002c
34
34
3.35
32.00 (0.58, 63.42)
Woodcock 1981
10
10
3.56
35.00 (4.54, 65.46)
Kurihara 1989
14
14
5.82
25.00 (1.17, 48.83)
Fujimoto 2002b
25
25
6.35
24.00 (1.19, 46.81)
McDonald 1995
26
26
7.88
21.00 (0.52, 41.48)
Eaton 2002
41
41
9.01
40.00 (20.85, 59.15)
Knebel 2000
33
33
16.35
5.49 (-8.73, 19.71)
Ishimine 1995
22
22
19.33
18.00 (4.93, 31.07)
Fujimoto 2002a
16
16
27.04
12.00 (0.95, 23.05)
Total (95% CI)
238
238
100.00
18.86 (13.11, 24.61)
Study
Favours placebo
Meters
95% CI
-50
0
50
Meters
95% CI
Weight
%
Favours oxygen
Supplementary Oxygen and Exercise
• Strong laboratory support for oxygen
improving exercise, by decreasing ventilation
• Funding criteria vary among jurisdictions
• Few controlled trials of oxygen during
exercise training
Supplemental Oxygen in hypoxemic COPD
700
6MWD (m)
600
500
400
300
200
100
0
Air
Oxygen
Rooyackers J, ERJ 1997;10:1278
Supplemental Oxygen in hypoxemic COPD
45
40
35
30
25
air
oxygen
20
15
10
5
0
CRQ
SWT
Garrod et al Thorax 2000;55:543
Supplemental Oxygen in Non-hypoxemic COPD
Work Rate (Watt)
70
60
B
50
40
A
30
20
0
5
10
15
20
Training Sessions
Emtner M, AJRCCM 2003;168
Supplemental Oxygen in Non-hypoxemic COPD
 Oxygen
 room air
Emnter. AJRCCM 2003;168:1034
Supplemental Oxygen in Non-hypoxemic COPD
Emnter. AJRCCM 2003;168:1034
Conclusion
1. LTOT is life saving for those with resting
hypoxaemia
2. Ambulatory oxygen should increase mobility
for those who require LTOT, but the evidence
to support this is incomplete
3. Oxygen for exercise training reduces
ventilation and may enable training at a higher
load.
OXYGEN
MEDICATION
LTX
Severe COPD
VENTILATORY
SUPPORT
LVRS
REHABILITATION
Chronic ventilatory support in COPD
• Why should we start NIPPV in COPD ?
• What is the evidence ?
• New studies
Sleep hypothesis
Run-in
O2
O2 + NIPPV
TST, min
203
260*
339*#
Efficiency, %
51
69*
81#
Awake, %
38
30
20*#
Meecham Jones et al.1995:152:538-544
Hyperinflation hypothesis
Diaz et al. ERJ 2002;20:1490
Short term randomised
controlled trials
Study
FEV1
PaCO2 BIpap
Effects
Strumpf 1991
0.54
49
15/2
Psych. 
Meecham
Jones 1995
0.86
56
18/2
Gay 1996
0.68
55
10/2
QOL
Gasex. 
Sleep 
=
Casanova2000 0.85
51
12/4
Psych.
Dysp. 
Outcome
Sample Treatment Treatment
effect
effect
FVC, L
33/33
Mean
-0.01
95 % CI
-0.14 , 0.13
Pimax, cm H2O
24/24
6.2
0.2 , 12.2
Pemax, cm H2O 24/24
18.4
-11.8 , 48.6
PaO2, mmHg
33/33
0.0
-3.8 , 3.9
PaCO2, mmHg
33/33
-1.5
-4.5 , 1.5
6-MWD, m
12/11
27.5
-26.8 , 81.8
Sleep eff., %
13/11
-4.0%
-14.7 , 6.7
Wijkstra et al. Chest 2003 ;124:337
Randomised controlled trials
Study
FEV1
PaCO2
BIpap
Monitoring
Strumpf 1991
0.54
6.5
15/2
no
Meecham
Jones 1995
0.86
7.4
18/2
ETCO2
Gay 1996
0.68
7.3
10/2
no
Casanova2000
0.85
6.7
12/4
No
Chronic ventilatory support in COPD
• Why should we start NIPPV in COPD ?
• What is the evidence ?
• New studies
OXYGEN
LTX
NUTRITION
COPD
LVRS
NIPPV
+
REHABILITATION
Ventilatory support during exercise
Oxygen
Ventilation
Dreher ERJ 2007;29:930
Ventilatory support during exercise
Dreher ERJ 2007;29:930
OXYGEN
LTX
NUTRITION
COPD
LVRS
NIPPV
+
REHABILITATION
Nocturnal NIPPV in stable COPD
Randomisation
NIPPV
12 weeks
12 weeks
Baseline
Measurements
3 months
NIPPV + PR
PR
Measurements
Measurements
Duiverman ATS 2008 abstract
Assessed for eligibility
(n= 87)
Not meeting inclusion
criteria (n= 15)
Randomised
(n =72)
Allocated to rehabilitation
(n=35)
Allocated to NIPPV + rehabilitation
(n= 37)
Early drop-outs (n=6)
- 2 died
- 2 withdrew
- 2 other diseases
Run in
Baseline
Baseline measurements
(n = 35)
Drop-outs (n=3)
noncompliant
3 months
Analysed
(n= 32)
Baseline measurements
(n = 31)
Drop-outs (n=7)
- 5 intolerance to NIPPV
- 1 noncompliant rehab
- 1 died
Analysed
(n = 24)
Patient characteristics
NIPPV+rehabilitation
Rehabilitation
Subjects, n
31
35
Age, yrs
63 ± 10
61 ± 7.4
BMI, kg/m2
27.1 ± 6.4
27.5 ± 6.3
FEV1, L
0.83 ± 0.37
0.77 ± 0.29
RV, % predicted 212 ± 43
223 ± 62
PaO2, kPa
7.89 ± 1.12
8.42 ± 1.25
PaCO2, kPa
6.81 ± 0.64
6.81 ± 0.76
Daytime blood gases
Baseline
After 3
Effect
95% CI
months
PaCO2, kPa
PaO2, kPa
N+R
6.9±0.7
6.4±0.7*
R
6.8±0.8
6.7±0.6
N+R
7.8±1.0
8.3±1.2*
R
8.3±1.3
8.3±0.9
29.2 ±2.3
28.4 ±2.4
R
29.4±2.7
29.1±1.8
N+R
4.6±2.0
3.6 ±1.9*
R
4.±2.1
4.1±1.4
N+R
7.39±0.03
7.40±0.02
R
7.40±0.03
7.40±0.03
HCO3 ,mmol/L N+R
BE, mmol/L
pH
-0.32
-0.6 to -0.1
0.25
-0.2 - 0.7
-0.90
-1.8 to 0.4
-0.66
-1.4 to 0.3
0.01
-0.01 to -0.02
Change in CRQ score (average per question)
Health related quality of life
CRQ
†
2.0
*
1.5
1.0
*
*
*
*
*
*
0.5
0.0
dys pnoe a fatigue e m otion m as te ry
total
MCID
Changes in MRF-28 scores (%)
Health related quality of life
MRF-28
†
†
10
0
-10
*
-20
*
-30
daily
*
cog
inv
total
Daily step count (steps/day)
Activities in daily living
Steps/day
15000
12500
*
10000
7500
5000
2500
0
Baseline
After 3 months
Rehabilitation
NIPPV + Rehabilitation
Chronic ventilatory support in COPD
• No strong evidence to provide ventilatory
to patients with COPD routinely.
• Ventilatory support during exercise might
improve its effects, although more studies
are needed
• Nocturnal ventilatory support improves the
effects of rehabilitation in hypercapnic
COPD patients.
Nocturnal blood gases
*
*
Muscle resting hypothesis
PaCO2, kPa
Sham NIPPV
baseline - 3 wk
7.4 - 7.3
NIPPV
baseline - 3wk
7.6 – 6.5
Ttot, s
3.4 -
3.3
2.9 -
3.6#
RV, % pred.
201 - 209
201 -
165#
TTdi
0.04 - 0.04
0.05 -
0.04
2.6
1.7#
PEEPi, cm H2O 2.6
- 2.7
-
Diaz et al. ERJ 2002;20:1490
Nocturnal NIPPV and daytime exercise training
<--------
P <0.009 -------- >
< P<0.01>
Garrod et al.AJRCCM 2000:162:1335
Noninvasive ventilation in stable
COPD
Lung After
function
Baseline
Effect 95% CI
Rehab
FEV1, L
N+R 0.90±0.38 0.89± 0.39 -0.04 -0.1 - 0.1
R
VC, L
N+R 2.89±0.82 2.98±0.89 -0.07 -0.3 - 0.2
R
RV%TLC
0.78±0.30 0.81±0.29
2.47±0.73 2.62±0.86
N+R
62±8
62±10
R
66±10
64±9
5.6±2.3
6.9±2.2*
5.3±2.2
5.9±2.3
PImax, kPa N+R
R
1
-3 - 5
0.8
-0.2 – 1.8
Noninvasive ventilation in stable
COPD
Breathing
pattern
Baseline After
Effect 95%CI
Rehab
VE, ml/ min
VT, ml
N+R
9.8 ± 3.0
10.6 ± 3.1
R
9.0 ± 1.9
8.6 ± 2.3
N+R
506 ± 144 560 ±135*
R
525 ± 129 519 ± 147
BF, breaths/ min N+R
R
20 ± 5
19 ±5
18 ± 4
17 ± 5
change
1.4
0.3 to 2.4
50
-9 to 116
0.5
-1.4 to 2.3
Shuttle walk test
<--------
P <0.009 -------- >
< P<0.01>
Garrod et al.AJRCCM 2000:162:1335
OXYGEN
LTX
NUTRITION
COPD
and hypercapnia
LVRS
NIPPV
+
REHABILITATION
Inclusion criteria
• COPD
• FEV1< 50% pred.
• symptoms : dyspnoea on exertion /
impaired exercise tolerance
• Age < 75 years
• PaCO2> 45 mmHg
Exclusion criteria
• Any diagnosis interfering with a
successfull rehabilitation
• OSAS : AHI > 10
• Currently on NIPPV
• Within last 2 years started a
rehabilitation programma
Design (1)
• Randomised open trial
• 2 arms :
NIPPV + rehabilitation (A)
rehabilitation alone (B)
• Duration :
24 months
Design (2)
0
inclusion / randomisation
3 m control period
3 m A : start NIPPV and after 2 weeks rehab
B : start rehabilitation
6 m end of clinical / outpatient rehab
6m
start follow-up rehabilitation community
Effect-parameters
• Primary
health related quality of life
• Secundary
dyspnoea
ADL activities
PSG
gasexchange
EMG respiratory muscles
freq./duur opnames
exacerbations freq.
exercise tolerance
MEASUREMENTS
CONTROL CLINICAL
0
3
HRQL
dyspneu
ADL
HRQL
dyspneu
ADL
PSG
BGA
EMG
SWT
LF
BGA
EMG
SWT
LF
6
COMMUNITY
12
24
HRQL
dyspneu
ADL
HRQL
dyspneu
ADL
PSG
HRQL
dyspneu
ADL
PSG
BGA
EMG
SWT
LF
BGA
EMG
SWT
LF
BGA
EMG
SWT
LF
Discussion
• No clear evidence for rationale of NIPPV
• Effect of NIPPV still controversial
• What did we learn ?
– Level of hypercapnia
– Adequate ventilatory support / monitoring
• What kind of research is needed in COPD ?
Conclusions
• Patients with neuromuscular diseases and
thoracic restriction have a good survival after
starting NIPPV/TIPPV
• The effects of NIPPV in COPD are still
controversial
• Combination of NIPPV and rehabilitation and
chronic NIPPV after NIPPV in the acute
setting are interesting areas for further
research
Chronic NIPPV in COPD
should be done in studies only
Effect of oxygen during endurance test
*
18
16
14
12
10
Room air
Oxygen
8
6
4
2
0
Emtner
Rooyackers
HELIOX
Laude AJRCCM 2006;173:865
HELIOX
Laude AJRCCM 2006;173:865
Medication
Heliox
IMT
Rehabilitation
in severe COPD
Oxygen
NM stimulation
ventilatory support
NIPPV during exercise
Van ‘t Hul ERJ 2006;27:65
NIPPV during exercise
Van ‘t Hul ERJ 2006;27:65
REsearch in COpd
the additional value of VEntilatory
support on Rehabilitation
RECOVER
Study design 2004-2008
Inclusion criteria
• COPD (GOLD 3 & 4)
• Symptoms : dyspnoea / exercise capacity 
• PaCO2> 45 mmHg
Randomised open study
• REHAB versus Rehab + night-time NIPPV
Primary outcome
• Health related QOL
RECOVER
Future Research
• Which patient is a good candidate for what type of
intervention
• Combination of strength training and NEMS
• Daytime NIPPV next to exercise
• Combining heliox and rehabilitation
• Life style studies to maintain initial effects
Baseline measurements
72 patients
Included
60 patients
Control period: 6
patients
Excluded after baseline
12 patients
Lost:
7 patients refused to
continue the study
5 patients died
1patient heart
failure
3 patients
OSAS
Rehabilitation: 42 patients
8 patients
PCO2<6.0 kPa/
>50%pred FEV1
Rehabilitation+
NIPPV:
20 patients
Rehabilitation: 22
patients
Baseline measurements
72 patients
Included
60 patients
Control period: 6
patients
Excluded after baseline
12 patients
Lost:
7 patients refused to
continue the study
5 patients died
1patient heart
failure
3 patients
OSAS
Rehabilitation: 42 patients
8 patients
PCO2<6.0 kPa/
>50%pred FEV1
Rehabilitation+
NIPPV:
20 patients
Rehabilitation: 22
patients
Bronchodilation and hyperoxia
Peters Thorax 2006;61:559
Reduction in Hyperinflation
Diaz et al. ERJ 2002;20:1490
Interval training (2)
FEV1 37% pred.
30 min/ dag
5 dag/week, 8 wk,
interval versus duu
Coppoolse ERJ 1999;14:258
Interval training (2)
Coppoolse ERJ 1999;14:258
Ventilatoire adaptatie
FEV1 1.9 L (56% pred)
5 dg/wk gedurende 8
wk
High = 80% AT
Low = 50% AT
45 min.
Casaburi et al. ARRD 1991;143:9
Ventilatoire adaptatie
Casaburi et al. ARRD 1991;143:9
Ventilatory support
and
Exercise training
Hakins Thorax 2002;57:853
Peripheral muscle weakness
Bernard et al. AJRCCM 1998;158:629
Training with oxygen
45
40
35
30
25
air
oxygen
20
15
10
5
0
CRQ
SWT
Garrod et al Thorax 2000;55:543
Exclusion criteria
• Any diagnosis interfering with a
successfull rehabilitation
• OSAS : AHI > 10
• Currently on NIPPV
• Within last 2 years started a
rehabilitation programma
RECOVER
Design (2)
0
inclusion / randomisation
3 m control period
3 m A : start NIPPV and thereafter rehabilitation
B : start rehabilitation
6 m end of clinical / outpatient rehab
6 m start follow-up rehabilitation community
Design (1)
• Randomised open trial
• 2 arms :
NIPPV + rehabilitation (A)
rehabilitation alone (B)
• Duration :
18 months
RECOVER
Effect-parameters
• Primary
health related quality of life
• Secundary
dyspnoea
ADL activities
PSG
gasexchange
EMG respiratory muscles
freq./duur opnames
exacerbations freq.
exercise tolerance
Medication
Exercise
IMT
Rehabilitation
in severe COPD
+
Oxygen
NM stimulation
ventilatory support
Medication
Exercise
IMT
Rehabilitation
in severe COPD
Oxygen
NM stimulation
ventilatory support
Cross sectional area of thigh muscle
Healthy
COPD
Bernard et al. AJRCCM 1998;158:629
Peripheral muscle weakness
Aerobic : 12 wk, 3d/wk
30 min, 80 % PWR
Strength : 12 wk,
60 % 1RM, 2 X 8 
80% 1RM, 3 X 8
Bernard et al. AJRCCM 1999;159:896
Neuromuscular electrical stimulation
•
•
•
•
COPD (FEV1 0.9 L)
NMES lower extremity
5 days/wk for 6 week (30 sessions)
Effects :
muscle function 
exercise capacity 
dyspnoea 
Neder Thorax 2002;57:333
Neuromuscular electrical stimulation
Neder et al. Thorax 2002;57:333
Rehabilitation and NEMS
Vivodtzev. Chest 2006;129:1540
Resistance training and testosteron
leg press fatigue
repetitions 25
+
*
20
*
placebo/no training
testosteron/no training
placebo/resistance
testosteron/resistance
15
10
5
0
baseline
week 10
Casaburi AJRCCM 2004;170:870
Resistance training and testosteron
constant work rate duration
min
9
8
7
6
placebo/no training
testosteron/no training
placebo/resistance
testosteron/resistance
5
4
3
2
1
0
baseline
week 10
Casaburi AJRCCM 2004;170:870
Rehabilitation and creatine
Loading phase
Rehabilitation
and
maintenance
Fuld Thorax 2005;60:531
Upper limb muscle function
repetitions
#*
16
14
12
#
10
8
6
creatine
placebo
#*
4
2
0
loading
rehabilitation
Fuld Thorax 2005;60:531
Endurance Shuttle Walk Test
SECONDS
400
350
300
250
creatine
placebo
200
150
100
50
0
loading
rehabilitation
Fuld Thorax 2005;60:531
Medication
Heliox
IMT
Rehabilitation
in severe COPD
Oxygen
NM stimulation
ventilatory support
PImax
6 or 12 MWD
Lotters ERJ 2004;20:570
FEV1 : 24% pred.
IMT :
40-50% PImax
30 min /day
5 /wk, 5 week
Ramirez-Sarmiento
AJRCCM
2002;166:1491
Exertional Oxygen in COPD
• 26 subjects, 73 yrs, FEV1 0.9L, resting PaO2 69
mmHg, PaCO2 41 mmHg
• 12 week cross over of air (6 weeks) versus oxygen (6
weeks) for activities
• 50% of patients preferred the 6 weeks on oxygen and
50% the 6 weeks on air
• No between group benefit to exercise tolerance,
quality of life or symptoms after 6 weeks
McDonald CF, AJRCCM 1995;152:1616
Domiciliary Oxygen and Quality of Life
Double blind randomized cross over of air versus oxygen during exertion, in 6 week
blocks. 26 subjects, age 73  6 yr, FEV1 0.9  0.4L, PaO2 69  9 mmHg, PaCO2 41 
3 mmHg
Baseline
Home Air
Home O2
Maximum Score
Dyspnea
Fatigue
Emotional
Function
Mastery
14 ± 5
17 ± 6
19 ± 6*
13 ± 4
15 ± 4
16 ± 4*
33 ± 9
35 ± 9
36 ± 8*
17 ± 6
19 ± 5†
20 ± 6*
35
28
49
28
* Home O2 compared with baseline (p<0.02)
† Mastery improved with home air compared with baseline (p<0.03). There was no significant difference
between oxygen and air
McDonald CF, AJRCCM 1995;152:1616
Sleep
(REM)
+
COPD
Decreased
Chemoresponses
+
Blunted
Chemoresponses
Hypopneas
and Apneas
+
High Paco2
Low Pao2
Rapid, Shallow
Breathing Pattern
Loss of Phasic
Intercostal Muscle
Activity
Loss of Intercostal
Muscle Tone
Aggravation of
blood gas
disturbances
Further
 VA
+
+
Increased Upper
Airway Resistance
Impaired Load
Compensation
Deterioration
of gas
exchange
High VD / VT
Impaired
Diaphragmatic
Function
+
High Intrathoracic
Airways Resistance
+
High Closing
Volume
 Paco2
 Pao2
 Sao2
Further
 V/Q
Phillipson EA, Chest 1984;85:24S
Non-invasive Positive Pressure Ventilation
(NIPPV) in COPD Patients with Chronic
Respiratory Failure (CRF)
• NIPPV might improve: sleep, gas exchange, muscle
function and mechanics
• Is there adequate evidence of effectiveness for NIPPV
in COPD?
• What might be valuable research questions?
NIPPV plus Oxygen versus Oxygen
alone for Hypercapnic COPD
14 patients with PaO2 45 ± 6 mmHg and PaCO2 56 ± 4 mmHg randomized to 3 months of LTOT
versus LTOT + NIPPV. Shown below is taken from Table 3 the effects on sleep, showing
improved sleep time, sleep efficiency and reduced wakefulness, with NPPV + LTOT.
TST, min
Efficiency, %
Awake, %
Run-in
203
O2
260*
O2 + NIPPV
339*#
51
38
69*
30
81#
20*#
Meecham-Jones J, 1995;152:538
NIPPV Plus Oxygen versus Oxygen
Alone for Hypercapnic COPD
75
75
60
60
PaCO2 (mmHg)
PaO2 (mmHg)
14 patients with PaO2 45 ± 6 mmHg and PaCO2 56 ± 4 mmHg randomized to 3 months of LTOT versus
LTOT + NIPPV. Below is Figure 1 showing mean values of daytime arterial PaO2 and PaCO2 at run in
and after 3 months of oxygen alone or oxygen plus NIPPV
45
30
0
45
30
Run-in
Oxygen
Alone
Oxygen
plus NPSV
0
Run-in
Oxygen
Alone
Oxygen
plus NPSV
Meecham-Jones J, 1995;152:538
NIPPV in Stable Hypercapnic COPD
36 patients randomized to NIPPV or sham for 3 hours per day, for 5 days a week for 3 weeks.
Below is taken from Table 2, showing a reduction in PCO2, lung volume, respiratory frequency
and intrinsic PEEP.
PaCO2, kPa
Ttot, s
RV, % pred
TTdi
PEEPi, cm H2O
Sham NIPPV
baseline - 3 wk
7.4 - 7.3
3.4 - 3.3
NIPPV
baseline - 3wk
7.6 - 6.5
2.9 - 3.6#
201 – 209
0.04 - 0.04
2.6 - 2.7
201 - 165#
0.05 - 0.04
2.6 - 1.7#
Diaz O, ERJ 2002;20:1490
NIPPV in Stable Hypercapnic COPD
36 patients randomized to NIPPV or sham for 3 hours per day, for 5 days a week for 3 weeks. Below
is taken from figure 3 showing the relationship between changes in PCO2 and dynamic intrinsic
positive end-expiratory pressure in control 0 and MIPPV 0 subjects
1
PaCO2 kPa
0
-1
-2
-3
-4
-3
-2
-1
0
1
2
3
PEEPi;dyn cmH2O
Diaz O, ERJ 2002;20:1490
Short Term RCT’s
Study
Strumpf, 1991
FEV1
0.54
PaCO2
49
BiPAP
15/2
Meecham-Jones, 1995
0.86
56
18/2
Gay, 1996
0.68
55
10/2
Casanova, 2000
0.85
51
12/4
Effects
Psych 
HRQL 
Gases 
Sleep 
Psych 
Dyspnea 
Sample
Treatment
Effect
Mean
Treatment
Effect
95% CI
FVC, L
33/33
-0.01
-0.14 , 0.13
Pimax, cm H2O
24/24
6.2
0.2 , 12.2
Pemax, cm H2O
24/24
18.4
-11.8 , 48.6
PaO2, mmHg
33/33
0.0
-3.8 , 3.9
PaCO2, mmHg
33/33
-1.5
-4.5 , 1.5
6MWD, m
12/11
27.5
-26.8 , 81.8
Sleep Efficiency %
13/11
-4.0%
-14.7 , 6.7
Outcome
Wijkstra P, Chest 2003;124:337
Short Term RCT’s
Study
Strumpf, 1991
FEV1
0.54
PaCO2
49
BiPAP
15/2
Meecham-Jones, 1995
0.86
56
18/2
Gay, 1996
0.68
55
10/2
Casanova, 2000
0.85
51
12/4
Effects
Psych 
HRQL 
Gases 
Sleep 
Psych 
Dyspnea 
Uncontrolled Trials
Study
Elliot
FEV1
0.53
PaCO2
60
BiPAP
15/2
Perrin
0.86
58
18/2
Sivasothy
Jones
0.70
0.90
64
61
10/2
12/4
Effects
BGA 
QoL 
BGA 
BGA 
BGA 
Short Term RCT’s
Study
Strumpf, 1991
FEV1
0.54
PaCO2
6.5
BiPAP
15/2
Monitoring
No
Meecham-Jones, 1995
Gay, 1996
Casanova, 2000
0.86
0.68
0.85
7.4
7.3
6.7
18/2
10/2
12/4
PETCO2
No
No
NIPPV Plus Oxygen versus Oxygen
Alone for Hypercapnic COPD
14 patients with PaO2 45 ± 6 mmHg and PaCO2 56 ± 4 mmHg randomized to 3 months of LTOT versus
LTOT + NIPPV. Shown below is taken from Figure 2 the correlation between change in daytime PaCO2
and change in night PtCO2
Daytime PaCO2 (mmHg)
10
8
6
4
2
0
-2
0
5
10
15
20
25
30
Nocturnal PtCO2 (mmHg)
Meecham-Jones P, 1995;152:538
Discussion
• No clear evidence for rationale of NIPPV
• Effect of NIPPV still controversial
• What did we learn?
– Level of hypercapnia
– Adequate ventilatory support
– Adequate monitoring
• Where does NIPPV fit in COPD management?
RCT of NIPPV Plus Physical Training in
Severe COPD
45 COPD patients (PaCO2 46mmHg) received 8 weeks of exercise training alone or with nightly NIPPV. Below
is taken from figure 2 showing changes in the shuttle walk test in both groups at each assessment. Changes
were manifested in the A3-A4 representing the 4 weeks from mid rehabilitation to post rehabilitation.
340
320
300
SWT
280
NPPV + ET
ET
260
240
220
200
180
160
140
A1
A2
A3
A4
Garrod R, et al. AJRCCM 2000;162:1335
Oxygen
Nutrition
LTX
COPD
with hypercapnia
NIPPV
LVRS
+
Rehabilitation
Enrollment
Inclusion
• COPD aged <75 years
• FEV1 <50% predicted
• Dyspnea on exertion and reduced exercise
tolerance
• PaCO2 >45 mmHg
Exclusion
• Co-morbidities influencing rehabilitation
• Obstructive Sleep Apnea: AHI >10
• Currently receiving NIPPV
• Rehabilitation within the last 2 years
Design
• Randomised 24 month open trial
• 3 months control
• 3 months NIPPV with facility supervised PR + 21 months
community supervised PR (A)
• 3 months facility supervised PR + 21 months community
supervised PR (B)
• Primary Outcome: Health related quality of life
• Secondary Outcomes: dyspnoea, activities of daily living,
gas exchange, exercise tolerance, exacerbation frequency
Rehabilitation and NIPPV
50
Hospital
Supervised
Rehabilitation
Control
Period
50
Community Based Rehabilitation
0
3
6
9
15
21
27
QoL
*
*
*
*
*
*
*
Cycle
Endurance
*
*
*
6MW
*
*
*
*
*
PFT
*
*
*
*
*
**
*
Night
Study
Home
visit
*
*
*
*
COPD Survivors Treated with NIPPV for Acute
Hypercapnic Respiratory Failure
110 patients survived NIPPV. After 1 year, 80% had been readmitted, 63% had a life threatening event
and 49% had died. Taken from figure 3 showing the probability of survival for patients who survived a
single episode of respiratory failure treated with NIPPV
Probability of Survival
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0
1
2
3
4
5
6
7
8
9 10 11 12
Time (months)
Chu C, et al. Thorax 2004;59:1020
Criteria
• COPD patients who required ventilation for
respiratory failure from AECOPD
• Ventilator free for at least 48 hours
• PaCO2 >45 mmHg at rest 55 mmHg
• Exclude: sleep apnea, heart failure, nonobstructive respiratory conditions
Design
• 24 month, randomised trial with 2 arms:
NIPPV and medication (A),
Medication only (B)
• Primary outcome - Survival
• Secondary outcome - health related quality of life,
hospital admission frequency, exacerbation
frequency, activities of daily living, gas exchange,
exercise tolerance
Conclusions
• The impact of NIPPV in COPD with chronic
respiratory failure remain controversial
• Two interesting areas are:
- Combination of NIPPV and PR versus PR alone
- Continued NIPPV after NIPPV used for AECOPD
• Wider use of NIPPV in COPD should await
evidence of effectiveness
Beademing tijdens inspanning
Zuurstof
Beademing
Dreher ERJ 2007;29:930
Zuurstof en dyspneu
Swinburn, ARRD 1991;143:913
Beademing en dyspneu
Dreher ERJ 2007;29:930
Duration of cycle endurance test
Dyspnoea end cycle endurance test
Chronic NIPPV in COPD
What is the rationale ?
• Sleep hypothesis
• Muscle resting hypothesis
• Hyperinflation hypothesis
Short term randomised
controlled trials
Study
FEV1
PaCO2 BIpap
Effects
Strumpf 1991
0.54
49
15/2
Psych. 
Meecham
Jones 1995
0.86
56
18/2
Gay 1996
0.68
55
10/2
QOL
Gasex. 
Sleep 
=
Casanova2000 0.85
51
12/4
Psych.
Dysp. 
Uncontrolled trials
Study
FEV1
PaCO2 BIpap
Effects
Elliot
0.53
8
15/2
BGA 
Perrin
0.86
7.8
18/2
QOL
BGA 
Sivasothy
0.70
8.6
10/2
BGA 
Jones
0.90
8.1
12/4
BGA 
Nocturnal hypoventilation
Meecham Jones et al.1995:152:538-544
Oxygen and dyspnoea
Dean ARRD 1992;146:941