Post on 14-Jan-2016
description
University Medical Centre Groningen
The Netherlands
Oxygen / ventilatory support in COPD
MEDICATION
OXYGEN
LTX
LVRS
REHABILITATION
VENTILATORY SUPPORT
Severe COPD
MEDICATION
OXYGEN
LTX
LVRS
REHABILITATION
VENTILATORY SUPPORT
Severe COPD
Cu
mu
lati
ve S
urv
ival %
Cu
mu
lati
ve S
urv
ival %
100100
00
Time (months)Time (months)
9090
8080
7070
6060
5050
4040
3030
2020
1010
00
1010 2020 3030 4040 5050 6060 7070 8080
NOTTNOTT
MRCMRC
19 hrs19 hrs
12 hrs12 hrs 15 hrs15 hrs
No OxygenNo Oxygen
Composite slide NOTT and MRC studiesComposite slide NOTT and MRC studies
203 subjects randomized to continuous or 12 203 subjects randomized to continuous or 12 hours of oxygen for at least 12 monthshours of oxygen for at least 12 months
87 subjects randomized to oxygen 87 subjects randomized to oxygen 15 hours/day or none15 hours/day or none
Dynamic Hyperinflation in COPDDynamic Hyperinflation in COPD
• Increases work of breathing from added elastic Increases work of breathing from added elastic loadsloads
• Respiratory muscles at a mechanical disadvantageRespiratory muscles at a mechanical disadvantage
• Contributes to the sensation of dyspnea with Contributes to the sensation of dyspnea with increasing increasing inspiratory pressuresinspiratory pressures
Modified fromModified from Somfay A, ERJ 2001;18:77 Somfay A, ERJ 2001;18:77
3232
1818
2020
2222
2424
2626
2828
3030
0.20.2 0.30.3 0.50.5 0.750.75 1.01.0
FiOFiO22
Resp
irato
ry r
ate
R
esp
irato
ry r
ate
(b
reath
/min
)(b
reath
/min
)
33
0.50.5
11
1.51.5
22
2.52.5
0.20.2 0.30.3 0.50.5 0.750.75 1.01.0
FiOFiO22
Insp
irato
ry c
ap
acit
y (
L)
Insp
irato
ry c
ap
acit
y (
L)
Effect of Oxygen in 10 Non-hypoxemic Patients with Severe COPD, During
Constant Work
22
44
66
88
1010
1212
1414
0.20.2 0.30.3 0.50.5 0.750.75 1.01.0
FiOFiO22
En
du
ran
ce t
ime (
min
)En
du
ran
ce t
ime (
min
)
Improves health-related quality of lifeImproves health-related quality of life
Increases exerciseIncreases exercise
Relieves dyspneaRelieves dyspnea
Reduces air trappingReduces air trapping
Reduces hyperinflationReduces hyperinflation
Reduces ventilationReduces ventilation
Medical Volume Reduction with OxygenMedical Volume Reduction with Oxygen
Exercise capacity – Endurance distance
StudyOxygen
N
Placebo
N
Meters
95% CIWeight
%Meters
95% CI
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)
-50-50 00 5050Favours placeboFavours placebo Favours Favours oxygenoxygen
Systematic Review of RCT’s of Short Term Benefit of Ambulatory Oxygen in COPD
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
Rooyackers J, ERJ 1997;10:1278
AirAir OxygenOxygen
707000
606000
505000
404000
303000
202000
101000
00
6M
WD
(m
)6M
WD
(m
)
Supplemental Oxygen in hypoxemic COPD
0
5
10
15
20
25
30
35
40
45
CRQ SWT
airoxygen
Garrod et al Thorax 2000;55:543
Emtner M, AJRCCM 2003;168Emtner M, AJRCCM 2003;168
Supplemental Oxygen in Non-hypoxemic COPDSupplemental Oxygen in Non-hypoxemic COPD
7700
6600
5500
4400
3300
2200 00 55 11
001155
2200Training Sessions
Work
Rate
(W
att
)
AA
BB
Supplemental Oxygen in Non-hypoxemic COPDSupplemental Oxygen in Non-hypoxemic COPD
Emnter. AJRCCM 2003;168:1034
Oxygen
room air
Emnter. AJRCCM 2003;168:1034
Supplemental Oxygen in Non-hypoxemic COPDSupplemental Oxygen in Non-hypoxemic COPD
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.
MEDICATION
OXYGEN
LTX
LVRS
REHABILITATION
VENTILATORY SUPPORT
Severe COPD
• Why should we start NIPPV in COPD ?
• What is the evidence ?
• New studies
Chronic ventilatory support in COPD
Sleep hypothesis
Run-in O2 O2 + NIPPV
TST, min 203 260* 339*#
Efficiency, %
Awake, %
51
38
69*
30
81#
20*#
Meecham Jones et al.1995:152:538-544
Diaz et al. ERJ 2002;20:1490
Hyperinflation hypothesis
Short term randomised controlled trials
Psych.Dysp.
12/4510.85Casanova2000
=10/2550.68Gay 1996
QOLGasex. Sleep
18/2560.86Meecham Jones 1995
Psych. 15/2490.54Strumpf 1991
EffectsBIpapPaCO2FEV1Study
Outcome 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
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
No12/46.70.85Casanova2000
no10/27.30.68Gay 1996
ETCO218/27.40.86Meecham Jones 1995
no15/26.50.54Strumpf 1991
MonitoringBIpapPaCO2FEV1Study
• Why should we start NIPPV in COPD ?
• What is the evidence ?
• New studies
Chronic ventilatory support in COPD
NUTRITION
OXYGEN
LTX
LVRS
REHABILITATION
NIPPV
COPD
+
Ventilatory support during exercise Ventilatory support during exercise
Oxygen Oxygen Ventilation Ventilation Dreher ERJ 2007;29:930
Dreher ERJ 2007;29:930
Ventilatory support during exerciseVentilatory support during exercise
NUTRITION
OXYGEN
LTX
LVRS
REHABILITATION
NIPPV
COPD
+
Nocturnal NIPPV in stable COPD
Measurements
Measurements
Measurements
12 weeks 12 weeks
NIPPV + PR
PR
Randomisation NIPPV
Baseline
3 months
Duiverman ATS 2008 abstract
Not meeting inclusion
criteria (n= 15)
Allocated to NIPPV + rehabilitation(n= 37)
Baseline measurements(n = 35)
Assessed for eligibility(n= 87)
Baseline
3 months
Analysed(n= 32)
Analysed(n = 24)
Drop-outs (n=3)noncompliant
Allocated to rehabilitation (n=35)
Baseline measurements(n = 31)
Randomised(n =72)
Early drop-outs (n=6)- 2 died- 2 withdrew - 2 other diseases
Drop-outs (n=7) - 5 intolerance to NIPPV- 1 noncompliant rehab- 1 died
Run in
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
Patient characteristics
Daytime blood gases Baseline After 3
months
Effect 95% CI
PaCO2, kPa N+R 6.9±0.7 6.4±0.7* -0.32 -0.6 to -0.1
R 6.8±0.8 6.7±0.6
PaO2, kPa N+R 7.8±1.0 8.3±1.2* 0.25 -0.2 - 0.7
R 8.3±1.3 8.3±0.9
HCO3 ,mmol/L N+R 29.2 ±2.3 28.4 ±2.4 -0.90 -1.8 to 0.4
R 29.4±2.7 29.1±1.8
BE, mmol/L N+R 4.6±2.0 3.6 ±1.9* -0.66 -1.4 to 0.3
R 4.±2.1 4.1±1.4
pH N+R 7.39±0.03 7.40±0.02 0.01 -0.01 to -0.02
R 7.40±0.03 7.40±0.03
Health related quality of lifeCRQ
Health related quality of lifeCRQ
dyspnoea fatigue emotion mastery total 0.0
0.5
1.0
1.5
2.0
*
*
*
* *
* *
†
MCID
Ch
ang
e in
CR
Q s
core
(av
erag
e p
er q
ues
tio
n)
Health related quality of life MRF-28
Health related quality of life MRF-28
daily cog inv total
-30
-20
-10
0
10
*
**
† †C
han
ges
in
MR
F-2
8 sc
ore
s (%
)
Activities in daily livingSteps/day
Baseline After 3 months0
2500
5000
7500
10000
12500
15000
*
NIPPV + Rehabilitation
Rehabilitation
Dai
ly s
tep
co
un
t (s
tep
s/d
ay)
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
Sham NIPPV
baseline - 3 wk
NIPPV
baseline - 3wk
PaCO2, kPa 7.4 - 7.3 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
PEEPi, cm H2O 2.6 - 2.7 2.6 - 1.7#
Diaz et al. ERJ 2002;20:1490
Nocturnal NIPPV and daytime exercise training
Garrod et al.AJRCCM 2000:162:1335
<-------- P <0.009 -------- >
< P<0.01>
Noninvasive ventilation in stable COPD
Lung function Baseline After
Rehab
Effect 95% CI
FEV1, L N+R 0.90±0.38 0.89± 0.39 -0.04 -0.1 - 0.1
R 0.78±0.30 0.81±0.29
VC, L N+R 2.89±0.82 2.98±0.89 -0.07 -0.3 - 0.2
R 2.47±0.73 2.62±0.86
RV%TLC N+R 62±8 62±10 1 -3 - 5
R 66±10 64±9
PImax, kPa N+R 5.6±2.3 6.9±2.2* 0.8 -0.2 – 1.8
R 5.3±2.2 5.9±2.3
Noninvasive ventilation in stable COPD
Breathing pattern Baseline After
Rehab
Effect 95% CI
change
VE, ml/ min N+R 9.8 ± 3.0 10.6 ± 3.1 1.4 0.3 to 2.4
R 9.0 ± 1.9 8.6 ± 2.3
VT, ml N+R 506 ± 144 560 ±135* 50 -9 to 116
R 525 ± 129 519 ± 147
BF, breaths/ min N+R 20 ± 5 19 ±5 0.5 -1.4 to 2.3
R 18 ± 4 17 ± 5
Shuttle walk test
Garrod et al.AJRCCM 2000:162:1335
<-------- P <0.009 -------- >< P<0.01>
NUTRITION
OXYGEN
LTX
LVRS
REHABILITATION
NIPPV
COPD
and hypercapnia
+
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 dyspnoeaADL activities PSG gasexchange EMG respiratory musclesfreq./duur opnamesexacerbations freq.
exercise tolerance
0 3 6 12 24
HRQL dyspneuADL
BGAEMG SWTLF
HRQL dyspneuADL PSG
BGAEMG SWTLF
HRQL dyspneuADL PSG BGAEMG SWTLF
HRQL dyspneuADL PSG BGAEMG SWTLF
HRQL dyspneuADL
BGAEMG SWTLF
MEASUREMENTS
CONTROL CLINICAL COMMUNITY
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
0
2
4
6
8
10
12
14
16
18
Emtner Rooyackers
Room airOxygen
*
HELIOX
Laude AJRCCM 2006;173:865
Laude AJRCCM 2006;173:865
HELIOX
Heliox
Medication
NM stimulation
ventilatory support
Oxygen
Rehabilitation
in severe COPD
IMT
Van ‘t Hul ERJ 2006;27:65
NIPPV during exercise
Van ‘t Hul ERJ 2006;27:65
NIPPV during exercise
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 measurements72 patients
Included60 patients
3 patients OSAS
8 patientsPCO2<6.0 kPa/
>50%pred FEV1
Excluded after baseline 12 patients
1patient heart failureControl period: 6
patients
Rehabilitation: 42 patients
Rehabilitation: 22 patients
Rehabilitation+ NIPPV: 20 patients
Lost:7 patients refused to continue the study5 patients died
Baseline measurements72 patients
Included60 patients
3 patients OSAS
8 patientsPCO2<6.0 kPa/
>50%pred FEV1
Excluded after baseline 12 patients
1patient heart failureControl period: 6
patients
Rehabilitation: 42 patients
Rehabilitation: 22 patients
Rehabilitation+ NIPPV: 20 patients
Lost:7 patients refused to continue the study5 patients died
Bronchodilation and hyperoxia
Peters Thorax 2006;61:559
Diaz et al. ERJ 2002;20:1490
Reduction in Hyperinflation
Interval training (2)
Coppoolse ERJ 1999;14:258
FEV1 37% pred.
30 min/ dag
5 dag/week, 8 wk,
interval versus duur
Interval training (2)
Coppoolse ERJ 1999;14:258
Casaburi et al. ARRD 1991;143:9
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
Ventilatory support
and
Exercise training
Hakins Thorax 2002;57:853
Peripheral muscle weakness
Bernard et al. AJRCCM 1998;158:629
Training with oxygen
0
5
10
15
20
25
30
35
40
45
CRQ SWT
airoxygen
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 dyspnoeaADL activities PSG gasexchange EMG respiratory musclesfreq./duur opnamesexacerbations freq.
exercise tolerance
Exercise
Medication
NM stimulation
ventilatory support
Oxygen
Rehabilitation
in severe COPD
IMT
+
Exercise
Medication
NM stimulation
ventilatory support
Oxygen
Rehabilitation
in severe COPD
IMT
Cross sectional area of thigh muscle
COPDHealthy
Bernard et al. AJRCCM 1998;158:629
Peripheral muscle weakness
Bernard et al. AJRCCM 1999;159:896
Aerobic : 12 wk, 3d/wk
30 min, 80 % PWR
Strength : 12 wk,
60 % 1RM, 2 X 8
80% 1RM, 3 X 8
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
Neder et al. Thorax 2002;57:333
Neuromuscular electrical stimulation
Vivodtzev. Chest 2006;129:1540
Rehabilitation and NEMS
Resistance training and testosteron
0
5
10
15
20
25
baseline week 10
placebo/no trainingtestosteron/no trainingplacebo/resistancetestosteron/resistance
Casaburi AJRCCM 2004;170:870
repetitions
leg press fatigue
*
*+
Resistance training and testosteron
0
1
2
3
4
5
6
7
8
9
baseline week 10
placebo/no trainingtestosteron/no trainingplacebo/resistancetestosteron/resistance
Casaburi AJRCCM 2004;170:870
min
constant work rate duration
Rehabilitation and creatine
Loading phase
Rehabilitation and
maintenance
Fuld Thorax 2005;60:531
Upper limb muscle function
0
2
4
6
8
10
12
14
16
loading rehabilitation
creatine
placebo
# *
Fuld Thorax 2005;60:531
repetitions
# *
#
Endurance Shuttle Walk Test
0
50
100
150
200
250
300
350
400
loading rehabilitation
creatine
placebo
Fuld Thorax 2005;60:531
SECONDS
Heliox
Medication
NM stimulation
ventilatory support
Oxygen
Rehabilitation
in severe COPD
IMT
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 LifeDouble 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
Dyspnea Fatigue Emotional Function
Mastery
Baseline 14 ± 5 13 ± 4 33 ± 9 17 ± 6
Home Air 17 ± 6 15 ± 4 35 ± 9 19 ± 5†
Home O2 19 ± 6* 16 ± 4* 36 ± 8* 20 ± 6*
Maximum Score 35 28 49 28
* * Home OHome O22 compared with baseline (p<0.02) compared with baseline (p<0.02)† † Mastery improved with home air compared with baseline (p<0.03). There was no Mastery improved with home air compared with baseline (p<0.03). There was no
significant difference between oxygen and airsignificant difference between oxygen and air
McDonald CF, AJRCCM 1995;152:1616
Phillipson EA, Chest 1984;85:24SPhillipson EA, Chest 1984;85:24S
SleepSleep(REM)(REM)
++ COPDCOPDDeteriorationDeterioration
of gasof gasexchangeexchange
Aggravation ofAggravation ofblood gasblood gas
disturbancesdisturbances
++
++
++
++
++
++
DecreasedDecreasedChemoresponseChemoresponse
ss
HypopneasHypopneasand Apneasand Apneas
Rapid, ShallowRapid, ShallowBreathing Breathing PatternPattern
Loss of PhasicLoss of PhasicIntercostal Intercostal
MuscleMuscleActivityActivity
Loss of Loss of IntercostalIntercostal
Muscle ToneMuscle Tone
FurtherFurther VVAA
FurtherFurther V/QV/Q
PacoPaco22
PaoPao22
SaoSao22
BluntedBluntedChemoresponsesChemoresponses
High PacoHigh Paco22
Low PaoLow Pao22
ImpairedImpairedDiaphragmaticDiaphragmatic
FunctionFunction
High IntrathoracicHigh IntrathoracicAirways ResistanceAirways Resistance
High ClosingHigh ClosingVolumeVolume
High VHigh VD D / V/ VTT
Increased UpperIncreased UpperAirway ResistanceAirway Resistance
Impaired LoadImpaired LoadCompensationCompensation
• 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?
Non-invasive Positive Pressure Non-invasive Positive Pressure Ventilation (NIPPV) in COPD Patients Ventilation (NIPPV) in COPD Patients with Chronic Respiratory Failure (CRF)with Chronic Respiratory Failure (CRF)
NIPPV plus Oxygen versus Oxygen alone for Hypercapnic COPD
Run-in O2 O2 + NIPPV
TST, min 203 260* 339*#
Efficiency, % 51 69* 81#
Awake, % 38 30 20*#
14 patients with PaO14 patients with PaO22 45 45 ± ± 6 mmHg and PaCO6 mmHg and PaCO22 56 ± 4 mmHg randomized to 3 56 ± 4 mmHg randomized to 3 months of LTOT versus LTOT + NIPPV. Shown below is taken from Table 3 the 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 effects on sleep, showing improved sleep time, sleep efficiency and reduced wakefulness, with NPPV + LTOT. wakefulness, with NPPV + LTOT.
Meecham-Jones J, 1995;152:538
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. 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
Meecham-Jones J, 1995;152:538
7575
6060
4545
3030
00Run-Run-
ininOxygeOxyge
n n AloneAlone
Oxygen Oxygen plus plus NPSVNPSV
PaC
OP
aC
O2
2 (m
mH
g)
(mm
Hg
)
7575
6060
4545
3030
00Run-Run-
ininOxygeOxyge
n n AloneAlone
Oxygen Oxygen plus plus NPSVNPSV
PaO
PaO
2
2 (m
mH
g)
(mm
Hg
)
NIPPV in Stable Hypercapnic COPD
Sham NIPPVbaseline - 3 wk
NIPPVbaseline - 3wk
PaCO2, kPa 7.4 - 7.3 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
PEEPi, cm H2O 2.6 - 2.7 2.6 - 1.7#
Diaz O, ERJ 2002;20:1490Diaz O, ERJ 2002;20:1490
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.
NIPPV in Stable Hypercapnic NIPPV in Stable Hypercapnic COPDCOPD36 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
Diaz O, ERJ 2002;20:1490Diaz O, ERJ 2002;20:1490
11
00
-1-1
-2-2
-3-3
-4-4 -3-3 -2-2 -1-1 00 11 22 33
PaC
OP
aC
O22 k
Pa
kP
a
PEEPi;PEEPi;dyndyn cmH cmH22OO
Short Term RCT’sStudy FEV1 PaCO2 BiPAP Effects
Strumpf, 1991 0.54 49 15/2 Psych
Meecham-Jones, 1995 0.86 56 18/2HRQL Gases Sleep
Gay, 1996 0.68 55 10/2 -
Casanova, 2000 0.85 51 12/4Psych
Dyspnea
Outcome Sample
Treatment EffectMean
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
Wijkstra P, Chest Wijkstra P, Chest 2003;124:3372003;124:337
Short Term RCT’sStudy FEV1 PaCO2 BiPAP Effects
Strumpf, 1991 0.54 49 15/2 Psych
Meecham-Jones, 1995 0.86 56 18/2HRQL Gases Sleep
Gay, 1996 0.68 55 10/2 -
Casanova, 2000 0.85 51 12/4Psych
Dyspnea
Uncontrolled TrialsStudy FEV1 PaCO2 BiPAP Effects
Elliot 0.53 60 15/2 BGA
Perrin 0.86 58 18/2QoL BGA
Sivasothy 0.70 64 10/2 BGA Jones 0.90 61 12/4 BGA
Short Term RCT’sStudy FEV1 PaCO2 BiPAP Monitoring
Strumpf, 1991 0.54 6.5 15/2 No
Meecham-Jones, 1995 0.86 7.4 18/2 PETCO2
Gay, 1996 0.68 7.3 10/2 No
Casanova, 2000 0.85 6.7 12/4 No
NIPPV Plus Oxygen versus Oxygen Alone for Hypercapnic COPD
Meecham-Jones P, 1995;152:538
14 patients with PaO14 patients with PaO22 45 45 ±± 6 mmHg and PaCO 6 mmHg and PaCO22 56 ± 4 mmHg randomized to 3 months of 56 ± 4 mmHg randomized to 3 months of LTOT versus LTOT + NIPPV. Shown below is taken from Figure 2 the correlation between LTOT versus LTOT + NIPPV. Shown below is taken from Figure 2 the correlation between change in daytime PaCOchange in daytime PaCO22 and change in night PtCO and change in night PtCO22
1010
88
66
44
22
00
-2-200 55 1010 1515 2020 2525 3030
Nocturnal PtCONocturnal PtCO22 (mmHg) (mmHg)
Dayti
me P
aC
OD
ayti
me P
aC
O22 (
mm
Hg
) (
mm
Hg
)
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 RCT of NIPPV Plus Physical Training in Severe COPD in Severe COPD
Garrod R, et al. AJRCCM 2000;162:1335
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.
340340
320320
300300
280280
260260
240240
220220
200200
180180
160160
140140A1A1 A2A2 A3A3 A4A4
SW
TS
WT NPPV + ETNPPV + ET
ETET
NutritionNutritionOxygen
LTX
LVRS
Rehabilitation
NIPPV
COPDCOPDwith with
hypercapniahypercapnia+
Enrollment
Exclusion
• Co-morbidities influencing rehabilitation
• Obstructive Sleep Apnea: AHI >10
• Currently receiving NIPPV
• Rehabilitation within the last 2 years
Inclusion
• COPD aged <75 years
• FEV1 <50% predicted
• Dyspnea on exertion and reduced exercise tolerance
• PaCO2 >45 mmHg
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
0 3 6 9 15 21 27
QoL * * * * * * *
Cycle Endurance
* * *Homevisit
6MW * * * * * *
PFT * * * * * * *
Night Study
** * *
50
Control Hospital
Supervised
RehabilitationPeriod
50 Community Based Rehabilitation
Chu C, et al. Thorax 2004;59:1020
COPD Survivors Treated with NIPPV for COPD Survivors Treated with NIPPV for Acute Hypercapnic Respiratory FailureAcute Hypercapnic Respiratory Failure110 patients survived NIPPV. After 1 year, 80% had been readmitted, 63% had a life 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 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 NIPPVfor patients who survived a single episode of respiratory failure treated with NIPPV
1.00.90.80.70.60.50.40.30.20.10.00 1 2 3 4 5 6 7 8 9 10 11 12
Time (months)Time (months)
Pro
bab
ilit
y o
f S
urv
ival
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, non-obstructive 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 Beademing tijdens inspanning
ZuurstofZuurstof BeademingBeademing Dreher ERJ 2007;29:930
Swinburn, ARRD 1991;143:913
Zuurstof en dyspneu
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
Psych.Dysp.
12/4510.85Casanova2000
=10/2550.68Gay 1996
QOLGasex. Sleep
18/2560.86Meecham Jones 1995
Psych. 15/2490.54Strumpf 1991
EffectsBIpapPaCO2FEV1Study
Uncontrolled trials
BGA 12/48.10.90Jones
BGA 10/28.60.70Sivasothy
QOLBGA
18/27.80.86Perrin
BGA 15/280.53Elliot
EffectsBIpapPaCO2FEV1Study
Nocturnal hypoventilation
Meecham Jones et al.1995:152:538-544
Oxygen and dyspnoea
Dean ARRD 1992;146:941