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Controversial Issues in NIV
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Controversial Issues in Non-Invasive Ventilation
Gamal Rabie Agmy, MD,FCCP
Professor of Chest Diseases
,Assiut University
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The normal ventilatory balance
Respiratory load Respiratory muscles
capacity
Ventilatory drive
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Respiratory Failure
Respiratory load
Respiratory muscles
capacity
Abnormal Ventilatory drive
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Mechanical ventilation unloads the
respiratory muscles
Respiratory load Respiratory muscles
Mechanical
ventilation
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NPPV: definition
Any form of ventilatory support applied without
the use of an endotracheal tube considered to
include:
*CPAP with or without pressure support
*Volume- and pressure- cycled systems
*Proportional assist ventilation (PAV).
AJRCCM 2001; 163:283-91
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Ventilators for NIV: Not all are useful in each indication
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Standard interfaces
Facial masks
advantages:
– sufficient ventilation also during mouth breathing
– sufficient ventilation in patients with limited co-operation
disadvantages:
– coughing is difficult
– skin lesions (bridge of the nose)
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Nasal masks
advantages:
– better comfort
– good seal
– coughing is possible
– communication is possible
disadvantages:
– effective in nose breathing only
– good co-operation is necessary
Standard interfaces
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Nasal prong/nasal pillow systems
* for patients with
claustrophobia
*for patients with allergies
against straps
*for low to moderate
pressures only
(< 20 cmH2O)
Standard interfaces
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total-face masks
• Safe interface for acute
respiratory
insufficiency with high pressures
• well tolerated by the patients
Standard interfaces
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helmet
• well tolerated by the patient
• no direct contact to the skin of
the face
• large dead space
• may influence the triggering of
the patient; use with CPAP
• very noisy
Standard interfaces
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mouthpieces
• simple and cheap
• short-interval alternative
interface for long-term
ventilated patients
Custom-made masks
• for long-term
ventilation
• if standard masks are
not tolerated
Standard interfaces
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Physiologic evaluation of three different
interfaces
cohort: 26 stable patients with hypercapnic COPD or interstitial lung disease.
intervention: three 30 minute tests in two ventilatory modes with
Conclusions: NIPPV was effective with all interfaces.
patients‘ tolerance: nasal mask > facial mask or nasal prongs
pCO2 reduction: facial mask or nasal prongs > nasal mask Navalesi P et al. Crit Care Med 2000;28:2139-2140
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Frequency of adverse effects and
complications of NIPPV
Mehta et al. Am J Respir Crit Care Med 2001;163:540-577
% occurrence
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Interfaces available for adults
Acute
respiratory
failure
Chronic
respiratory
failure
Facial mask 63% 6%
Nasal mask 31% 73%
Nasal prongs 6% 11%
Mouth piece 0% 5%
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THE RATIONALE
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LV failure
Pulmonary
edema
Pulmonary
compliance
Airway
resistance
Negative
Intrathoracic
Pressure Swing
Work of
breathing
CO
PaO2 Respiratory
muscle
fatigue
DaO2
+
PaCO2
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LV failure
Pulmonary
edema
Pulmonary
compliance
Airway
resistance
Negative
Intrathoracic
Pressure Swing
LV
transmural
pressure
O2
Cost of
breathing
LV afterload
+
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Rasen et al: Chest 1985; 87: 158-162
Negative intrathoracic pressure swings during CPE
Pes (cmH20)
0
-20
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IntraThoracicPressure
and
LV function
AO
LV
ITP effort = ITP = Ptm
LV afterload
100
-20
Ptm = 100-(-20) = 120
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CPAP IN CPE
Rasen et al: Chest 1985; 87: 158-162
Pes
(cmH20)
0
-20
Spontaneous breathing CPAP 15 cmH20
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IntraThoracicPressure
and
LV function
AO
LV
ITP effort = ITP = Ptm
LV afterload
100
-5
Ptm = 100-(-5) = 105
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Rationale of positive pressure ventilation in CPE
Positive Pressure
ITP FRC
Pre-load Venous return
LVafterload PTM
PaO2 WOB
Cardiac performance pulmonary congestion
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CPAP Standard treatment
total intubated died total intubated died mortality intubation
rate
Rasasen, 1985
20 6 3 20 12 6 -15% -30%
Bersten,
1991
19 0 2 20 7 4 -9.5% -35%
Lin, 1995 50 8 4 50 18 6 -4% -20%
89 14 9 90 37 16 -6.6% -26%
CPAP vs. standard treatment in acute pulmonary oedema
Pang D et al.: Chest 1998; 114: 1185-92
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• Multi-centre, randomized, prospective study with
130 patients with respiratory insufficiency.
• Setting: emergency room.
• Intervention: standard treatment with drugs and
high flow oxygen versus
standard treatment and NIV (nPSV).
Noninvasive Ventilation in Cardiogenic Pulmonary Edema A Multicenter Randomized Trial
Nava S, et al. Am J Respir Crit Care Med 2003;168:1432-1437
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Noninvasive Ventilation in Cardiogenic Pulmonary Edema A Multicenter Randomized Trial
Nava S, et al. Am J Respir Crit Care Med 2003;168:1432-1437
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Results:
• Similar intubation rate in both arms.
• Patients receiving NIV had a significantly better improvement
of PaO2/FiO2 within the first 30 minutes and within the first 3
hours of treatment.
• Hypercapnic patients: Significantly shorter time to
normalisation of PaCO2; lower intubation rate with NIV (2/33
vs. 9/33).
• Hypocapnic patients: Significantly higher intubation-
frequency.
Noninvasive Ventilation in Cardiogenic Pulmonary Edema A Multicenter Randomized Trial
Nava S, et al. Am J Respir Crit Care Med 2003;168:1432-1437
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Noninvasive Ventilation in Cardiogenic Pulmonary Edema A Multicenter Randomized Trial
Nava S, et al. Am J Respir Crit Care Med 2003;168:1432-1437
Pi 14,5 ± 21,1 mbar; Pe 6,1 ± 3,2 mbar mean ventilation time: 11,4 ± 3,6 hrs
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Multicentre clinical trial: Noninvasive ventilation in
acute cardiogenic pulmonary edema.
Gray A , et al. N Engl J Med. 2008 Jul 10;359(2):142-51.
primary endpoint:
death within 7 days
primary endpoint:
death or intubation within 7 days
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Multicentre clinical trial:
Noninvasive ventilation in
acute cardiogenic pulmonary edema.
Gray A , et al. N Engl J Med. 2008 Jul 10;359(2):142-51.
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Intervention
*Standard nitrate, diuretic and opioid therapy
*Consent + Randomised for 2 hours to:
-Standard oxygen therapy (by facial mask)
-CPAP (5 cmH2O to a max 15 cmH2O)
-NIPPV (8/4 cmH2O to a max 20/10 cmH2O)
*Fi02 0.6
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Primary Outcome: Mortality Standard
Therapy
Non-
Invasive
Ventilation
OR
95% CI
P Value
7-Day
9.8%
9.5%
0.97
0.63 -
1.48
0.869
30-
Day
16.7%
15.4%
0.93
0.65 -
1.32
0.685
7-day mortality, non-recruited 9.9%
No interaction with disease severity
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NIV in Stable COPD:
Pro
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Zeit (Tage)
1 2 3 5 9
B G A
(m m H g)
30
40
50
60
70
80
90
100
Zeit (Tage)
1 2 3 5 9
B G A
(m m H g)
30
40
50
60
70
80
90
100
PaC O 2
PaO 2
Windisch W. et al. Respir Med 2002; 96:572-579
Days
mmHg
NPPV (assPCV)
- mean IPAP 30 ±4 mbar
- mean bf 23 ±2 /min
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Tim e after cessation of nocturnal NPPV
baseline 0 0,5 1 3 7 11 15
Pa
CO
2 d
urin
g s
po
nta
ne
ou
s b
re
ath
ing
46
48
50
52
54
56
58
[hours]
[m m Hg]
P < 0.001
P = 0.26
PaCO2
Windisch W. et al. Respir Physiol Neurobiol 2006; 150:251-260
NPPV (assPCV)
- mean IPAP 31 ±7 mbar
- mean bf 21 ±2 /min
NPPV Controls
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Tim e after cessation of nocturnal N PPV
baseline 0 0,5 1 3 7 11 15
VT
du
rin
g s
po
nta
ne
ou
s b
re
ath
ing
0,50
0,55
0,60
0,65
0,70
[L]
[hours]
P = 0.28
P < 0.05
Windisch W. et al. Respir Physiol Neurobiol 2006; 150:251-260
Tidal volume
NPPV Controls
NPPV (assPCV)
- mean IPAP 31 ±7 mbar
- mean bf 21 ±2 /min
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Windisch W. et al. Chest 2005; 128:657-662
NPPV (assPCV)
- mean IPAP 28 ±6 mbar
- mean bf 21 ±3 /min
2-year survival: 86%
N = 34
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Budweiser S. et al. Respir Care 2006; 51:126-132
BMI <20 kg/m2 = 21%
N = 141
NPPV (assPCV)
- mean IPAP 20 ±4 mbar
- mean bf 20 ±4 /min
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Severe Respiratory
Insufficiency Questionnaire
SRI
ATS homepage:
http://www.atsqol.org/sections/instruments/pt/pages/sri.html
Windisch W. et al. J Clin Epidemiol 2003; 56:752-759 Windisch W. et al. J Clin Epidemiol 2008; 61:848-853
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T0 (baseline) T1 T12 Months
• Multicenter Study (N = 135)
• Outcomes: - Quality of life (SF-36; SRI)
- Side effects
- Hospitalisations
- Compliance
- Physiological parameters
Windisch W. Eur Respir J 2008; 32:1328-1336
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45
55
65
T0 T1 T12
COPD
Restriktiv
Neuromuskulär
Changes in SRI-SS
independent from the underlying disease
MANOVA; F=0,62; P=0,65.
P < 0.001 COPD
P < 0.001 neuromuscular
P < 0.001 restrictive thoracic
45
55
65
T0 T1 T12
COPD RTD NMD
SR
I-S
um
mary S
cale
(S
RI-S
S)
IPAP/EPAP (mbar)
20/3
19/4
25/1
Windisch W. Eur Respir J 2008; 32:1328-1336
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suppl. O2 (2.3 L/min) suppl. O2 (2.3 L/min) + NPPV (29/4 mbar, 20/min)
Dreher M. et al. Eur Respir J 2007; 29: 930-936
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suppl. O2 suppl. O2 + NPPV
PaCO22 (mmHg)
50 53 50 51 P < 0.001 N.S.
Six-minute walking test
BDS
Walking distance (m)
6 4 P < 0.001
209 252 P < 0.05
Dreher M. et al. Eur Respir J 2007; 29: 930-936
m ean before after m ean
Pa
O2 (
mm
Hg
)
50
60
70
80
90
100
110P < 0.001
m ean before after m ean
Pa
O2
(m
mH
g)
45
50
55
60
65
70
75
80
85 P < 0.001
PaO
2 (
mm
Hg)
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Rehab
Rehab + NPPV
Duiverman ML. et al. Thorax 2008; 63:1052-1057
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ERS Congress 2008 in Berlin
A randomised trial of home non-invasive ventilation vs. sham
ventilation in survivors of acute hypercapnic respiratory failure
in COPD.
Chu CM et al. Eur Respir J 2008; 32(Suppl.52):38s.
•42 COPD patients were randomised to receive either NPPV or sham
ventilation following acute NIV
• At days 120 patients were free of acute hypercapnic respiratory failure:
• 81% NPPV group
• 33% sham ventilation
Nocturnal non-invasive positive pressure ventilation (NIPPV) in
stable hypercapnic COPD patients – a randomized controlled
trial. Funk GC et al. Eur Respir J 2008; 32(Suppl.52):37s.
• 26 COPD patients received NIPPV over 6 months following mechanical ventilation on
the ICU
• After 6 months patients were randomised to stop NIPPV or to continue NPPV
• Discontinuation of NIPPV caused clinical worsening (resumption of NPPV or ICU
admission)
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NIV in Stable COPD:
con
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Home NIV not recommended
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(Casanova et al Chest 2000;118:1582-90)
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Clini E. et al. Eur Respir J 2002; 20:529-538
Hospitalisation following NPPV-establishment
LTOT: +27%
NPPV + LTOT: -45%
ICU-Admission following NPPV-establishment
LTOT: -20%
NPPV + LTOT: -75% n.s
n.s
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mesi
SURVIVAL NPPV
LTOT
THE ITALIAN MULTICENTRE STUDY ON
NONINVASIVE POSITIVE PRESSURE VENTILATION
IN COPD PATIENTS
Clini et al ERJ 2001
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COPD
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HOSPITAL ADMISSIONS
0
0,5
1
1,5
2
2,5
3
3,5
4
Follow-back
Follow-up
Total hospital admissions (nr/pt/year)
0
0,5
1
1,5
2
ICU admissions (nr/pt/year)
NPPV LTOT NPPV LTOT Clini et al ERJ 2001
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Nocturnal NIPPV for at least three months in hypercapnic patients
with stable COPD had no consistent clinically or statistically
significant effect on lung function, gas exchange, respiratory muscle
strength, sleep efficiency or exercise tolerance.
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Current evidence about the therapeutic benefit of
mechanical ventilation is weak, but consistent,
suggesting alleviation of the symptoms of chronic
hypoventilation in the short term, and in two small
studies survival was prolonged. Mechanical ventilation
should be offered as a therapeutic option to patients
with chronic hypoventilation due to neuromuscular
diseases.
Annane, D; Chevrolet, JC; Chevret, S; Raphael, JC
Nocturnal mechanical ventilation for chronic
hypoventilation in patients with neuromuscular and chest
wall disorders.
Cochrane Database of Systematic Reviews. Issue 1, 2001
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v
v
IPS 16 cmH2O
PEEP 3 cmH2O
IPS 15 cmH2O
PEEP 3 cmH2O
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K. Marquis et al. AJRCCM 2002; 166:809-813
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S. Bernard et al. AJRCCM 1998; 158:629-634
NORMAL COPD
Surface 118.5 cm2 Surface 79.6 cm2
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Exercise in COPD patients: PSV reduces inspiratory effort
Maltais et al. Am J Respir Crit Care Med, 1995; 151:1027
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PSV 10 cmH2O ( )
PSV 5 cmH2O ( )
van 't Hul et al ERJ 2006
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Lack of additional effect of adjunct of assisted ventilation to
pulmonary rehabilitation in mild COPD patients
L. Bianchi, K. Foglio, R. Porta, P. Baiardi, M. Vitacca, N. Ambrosino
“Assisted ventilation
during training
sessions…., was not well
tolerated by all patients
and gave no additional
physiological benefit in
comparison with exercise
training alone.“
Respiratory Med, 2002; 96:359-367
PAV
SB
40
50
60
70
80
90
100
110
120
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Training session (days)
Tra
inin
g i
nte
nsi
ty
(% P
eak
Work
rate
)
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No clinically or statistically significant effect on survival,
hospital admission, lung function, respiratory muscle strength
As an adjunct to exercise training in selected patients with
severe COPD, NIV may produce modest additional
improvements in exercise performance
Future research should primarily focus on adequate patient
selection and recognition of the mechanisms through which NIV
may work
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Severe acute hypoxemic respiratory failure
• Heterogeneous clinical condition • Results of studies on NIV unrelated to CPE are
inconsistent
Main goal of NIV: Avoid ETI
Severe AHRF Often need ETI-IMV
Improved morbidity and mortality?
IMV morbidity and mortality
Avoidance of endotracheal intubation
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Severe Community-Acquired Pneumonia
Major criteria • Mechanical ventilation
• Septic shock
Minor criteria • Respiratory rate >30 min-1 • PaO2/FiO2 <250 • Bilateral or multilobar • SBP <90 mmHg * • BUN >25 • Platelets <100,000 • Leukocytes <4,000 • Confusion • Hypothermia
Clin Infect Dis. 2007;44 Suppl 2:S27-S72
1 Major or 3 Minor Criteria
Pneumonia is associated with poor outcome in patients
receiving NIV
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NIV in acute COPD: correlates for success
Retrospective analysis 59 episodes of ARF in 47
COPD patients • NIV success: 46 • NIV failure: 13
Predictors for NIV failure: • Higher PaCO2 at admission • Worse functional condition • Reduced treatment
compliance
• Pneumonia Ambrosino N. Thorax 1995;50:755-7
NIV failure
O ther Pneum onia
%
0
20
40
60
n=8
p=0.019n=5
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NIV failure in acute hypoxemic respiratory failure
Antonelli M. Intensive Care Med 2001; 27: 1718-28
• Eight ICUs • n=354:
• Success: 246 • Failure: 108
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Non-invasive ventilation and pneumonia
Conclusion: Patients with pneumonia causing ARF and
needing NIV are among those with worst outcome
but, …..
is NIV effective in patients with pneumonia?
???
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NIV in severe community-acquired pneumonia
Prospective, randomised, controlled
Severe CAP (ATS criteria).
Standard treatment vs ST + NPPV. n: 28 + 28 = 56
Confalonieri M. Am J Respir Crit Care Med 1999;160:1585-91
O verall population
N IV C ontro l
%
0
20
40
60p=0.03
n=6
n=14
C O PD +
H ypercapnia
N IV C ontro l
%
0
20
40
60
N on-C O PD +
N on-hypercapnia
N IV C ontro l
0
20
40
60
n=0
n=6
n=6
n=8
p=0.005p=0.73
In tubation rate
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NIV in severe community-acquired pneumonia
O verall population
N IV C ontro l
%
0
20
40
60
p=N S
n=7
n=10
C O PD +
H ypercapnia
N IV C ontro l
%
0
20
40
60
N on-C O PD +
N on-hypercapnia
N IV C ontro l
0
20
40
60
p=0.05p=0.71
n=1
n=5
n=6
n=5
2-m onth m ortality
Shorter length of stay only in COPD patients with hypercapnia
Confalonieri M. Am J Respir Crit Care Med 1999;160:1585-91
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CPAP in severe hypoxemic ARF
Delclaux C. JAMA 2000;284:2352
R espiratory rate
B aseline 60' after
20
30
40
C PA P + O2
O2 a lone
PaO 2/F iO 2
B aseline 60' after
100
150
200
250
p<0.001
p<0.001
Intubation
123 patients: 54% pneumonia, 34% cardiac disease • 34/62 CPAP + O2 • 33/61 O2 alone
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O verall population
N IV C ontro l
%
0
20
40
60
80
100
p=0.010
n=13
n=28
Pneum onia
N IV C ontro l
%
0
20
40
60
80
100
Cardiogenic
pulm onary edem a
N IV C ontro l
%
0
20
40
60
80
100
A LI/A R D S
N IV C ontro l
0
20
40
60
80
100
Thoracic traum a
N IV C ontro l
0
20
40
60
80
100
n=5
n=11
n=1n=2
n=6
n=1
n=5
n=8p=0.017
p=0.467
p>0.999
p=0.333
NIV in severe AHRF: Intubation rate
Ferrer M et al. Am J Respir Crit Care Med 2003;168:1438
Prospective, randomised, controlled, 3 centres
N=105. Pneumonia: 34 (32%)
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O verall population
N IV C ontro l
%
0
20
40
60
80
100
p=0.028
n=9
n=21
Pneum onia
N IV C ontro l
%
0
20
40
60
80
100
Cardiogenic
pulm onary edem a
N IV C ontro l
%
0
20
40
60
80
100
A LI/A R D S
N IV C ontro l
0
20
40
60
80
100
Thoracic traum a
N IV C ontro l
0
20
40
60
80
100
n=3
n=8
n=1n=2
n=5
n=0
n=3
n=7p=0.030
p=0.569
p>0.999 p=0.515
NIV in severe AHRF: ICU mortality
Ferrer M et al. Am J Respir Crit Care Med 2003; 168:1438
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NIV as an alternative to ETI in severe AHRF
Antonelli M et al. N Engl J Med 1998;339:429-35
Patients with ETI predefined criteria
NIV vs intubation+IMV
In tubated patients
%0 20 40 60 80 100
ETI-IM V
N IVp<0.001n=11
n=32
Pneum onia
(% )
0
10
20
30
Sinusitis
N IV
ETI-IM V
n=1
n=8
n=0
n=2
p<0.01
Patients w ith com plications
N IV ETI-IM V
%
0
20
40
60
80 p<0.05
n=12
n=21
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NIV in immunosuppressed patients with pulmonary infiltrates and AHRF
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NIV in immunosuppressed patients with pulmonary infiltrates and ARF
• Early administration of NIV: 26 NIV vs 26 control – Haematological + neutropenia (BMT, chemotherapy)
– Immunosuppressor therapy (transplant, steroids)
– AIDS
In tubation
N IV C ontro l
(% )
0
20
40
60
80
100
H ospital m ortality
N IV C ontro l
0
20
40
60
80
100p=0.03 p=0.02
Hilbert G. N Engl J Med 2001;344:481
NIV vs control:
• Faster improvement of hypoxemia
• Less severe complications
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NIV in ARF after solid organ transplant
• Solid organ transplant: lung, liver, renal
• Incidence of ARF in postop. period: 21%
• Patients: 20 NIV vs 20 control
In tubation
N IV C ontro l
(% )
0
20
40
60
80
100
IC U m ortality
N IV C ontro l
0
20
40
60
80
100p=0.002
p=0.05
Antonelli M. JAMA 2000;283:235
NIV vs control:
• Faster improvement of hypoxemia
• Less severe complications
• Hospital mortality unchanged
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NIV in AHRF: A systematic review
• RCTs on standard treatment with and without NIV
• Not due to cardiogenic pulmonary oedema
Endotracheal intubation ICU mortality
Absolute risk reduction: 23% (10-35%) Absolute risk reduction: 17% (8-26%) Trial results significantly heterogeneous
Keenan S. Crit Care Med 2004;32:2516
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Why is NIV more effective than CPAP in severe hypoxemic ARF?
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Physiologic effect of CPAP and NIV in ALI-ARDS 10 patients with indication for NIV Short-term effects of:
• CPAP 10 cmH2O • 2 combinations of NIV: PSV 10–PEEP 10; PSV 15-PEEP 5
L’Her E. Am J Respir Crit Care Med 2005;172:1112-8
Respiratory rate
In itial
CPAP-10
PSV 10-10
PSV 15-5Final
26
28
30
32
34 PaO 2/F iO 2
In itial
CPAP-10
PSV 10-10
PSV 15-5Final
120
150
180
210
240
270
* **
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CPAP and NIV in ALI-ARDS: Work of breathing, neuromuscular drive and dyspnea
L’Her E et al. Am J Respir Crit Care Med 2005;172:1112-8
PSV + PEEP is needed to reduce inspiratory muscle effort
CPAP improves oxygenation but fails to unload the respiratory muscles
PSV levels of 10 and 15 cmH2O provide similar unloading but differ in their effects on dyspnea
PTPdi
In itial
CPAP-10
PSV 10-10
PSV 15-5Final
100
200
300
400
P 0.1
In itial
CPAP-10
PSV 10-10
PSV 15-5Final
1
2
3
4
*
**
*
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Different efficacy of NIV in severe pneumonia (no hypercapnia, no COPD)
Confalonieri'99NIV G roup
Control G roupConfalonieri'99
AP
AC
HE
-II
0
5
10
15
20
25
Ferrer'03S
AP
S-I
I
0
10
20
30
40
Ferrer'03
Pa
O2/F
iO2
0
50
100
150
200
p=0.05
Arterial hypoxem ia Baseline severity
Ferrer'03
%
0
20
40
60
80
C onfalonieri'99 Ferrer'03
0
20
40
60
C onfalonieri'99
p<0.05
ET Intubation H ospital m ortality
p<0.05
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Don’t forget contraindications for NIV
Need for immediate intubation: • Cardiac or respiratory arrest • Respiratory pauses + alertness + gasping • Psychomotor agitation sedation • Massive aspiration • Inability to manage secretions
Other limitations for NIV: • Severe non-respiratory organ failure • Face surgery, trauma or deformity • Upper airway obstruction • Inability to cooperate/protect the airways
Am J Respir Crit Care Med 2001;163:283-91
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Ventilators for NIV: Not all are useful in each indication
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Summary
Lower likelihood to need ETI when NIV is added to standard medical treatment in severe AHRF
Effects of NIV on mortality are less evident
Different efficacy of NIV among different populations:
Pneumonia with severe hypoxemia and causing COPD exacerbation
The routine use of NIV in all patients with severe AHRF is not supported
CPAP: No evidences on benefits in AHRF (post-op excluded)
Facilities for close monitoring and rapid intubation are advised
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ERS Postgraduate Course NIV
Hannover 2009
NIV in Acute Respiratory Failure
CONTRA
• Acute Respiratory Failure could have
different pathophysiology
• Clinical Studies does not reflect real life and
exclude the more severly ill patients
• NIV in hypoxemic patients cause potential
harm, the risk-benefit-ratio is not positive
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ERS Postgraduate Course NIV
Hannover 2009
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ERS Postgraduate Course NIV
Hannover 2009
• Conclusion: Randomized trials suggest that patients with acute
hypoxemic respiratory failure are less likely to require endotracheal intubation when NPPV is added to standard therapy. However, the effect on mortality is less clear, and the heterogeneity found among studies suggests that effectiveness varies among different populations.
As a result, the literature does not support the routine use of NPPV in all patients with acute hypoxemic respiratory failure.
Crit Care Med 2004; 32:2516 –2523
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ERS Postgraduate Course NIV
Hannover 2009
NIV in Acute Respiratory Failure
• Meta-Analysis of RCT of patients with acute hypoxemic respiratory failure not due to cardiogenic pulmonary edema
• interventions compared noninvasive ventilation and standard therapy with standard therapy alone
• outcomes included
– need for endotracheal intubation,
– length of intensive care unit or hospital stay
– intensive care unit or hospital survival.
Author Year No.of pts
Wysocki 1995 41
Confalioneri 1999 33 (out of 56)
Martin 2000 32 (out of 61)
Antonelli 2000 31 (out of 40)
Hilbert 2001 52
Ferrer 2003 75 (out of 105)
Auriant 2001 48
Keenan SP. Crit Care Med 2004; 32:2516 –2523
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ERS Postgraduate Course NIV
Hannover 2009
Risk of Endotracheal Intubation Length of ICU Stay
Keenan SP. Crit Care Med 2004; 32:2516 –2523
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ERS Postgraduate Course NIV
Hannover 2009
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ERS Postgraduate Course NIV
Hannover 2009
NIV in immunosuppressed patients
• Randomized trial in 52 immunosuppressed patients with pulmonary infiltrates, fever and hypoxemic respiratory failure
• Group A: Standard treatment (Antimicrobial agents, diuretics, bronchodilators, immunosuppressive agents, heparine s.c.)
• Group B: Standard + NIPPV
NIPPV Setting: Vt 7 ml/kg, PEEP til 10 cm H2O duration of NIPPV: at least 45 min. every 3 hours
Hilbert G et al. N Engl J Med 2001; 344: 481-7
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ERS Postgraduate Course NIV
Hannover 2009
NIV in immunosuppressed patients
Outcome NIV Standard p RR
Intubation 12/26 20/26 0.03 0.60
initial improve in
pO2 / FiO2
12 4 0.02
sustained improve in
pO2 / FiO2
13 5 0.02
death on ICU 10/26 18/26 0.03 0.56
death in hospital 13/26 21/26 0.02 0.62
Death in the hospital
Hilbert G et al. N Engl J Med 2001; 344: 481-7
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ERS Postgraduate Course NIV
Hannover 2009
NIV in immunosuppressed patients
• Exclusion Criteria
– hemodynamic instability (RRsyst < 80 mmHg)
– ECG: Ischemia or ventricular arrhythmia
– cardiac failure
– COPD
– pCO2 > 55 mmHg, pH < 7.35
– multiorgan failure
– deterioration in neurological status (GCS < 8)
Hilbert G et al. N Engl J Med 2001; 344: 481-7
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ERS Postgraduate Course NIV
Hannover 2009
Patient Demographics:
• Pneumonia (34)
• Cardiogenic Pulmonary Oedema (30)
• Thoracic trauma (17)
• ARDS (15)
• others (9)
Severe Hypoxemic Respiratory Failure
Basic Disease
Ferrer M, et al. Am J Respir Crit Care Med 2003;168:1438-1444
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ERS Postgraduate Course NIV
Hannover 2009
0
20
40
60
80
100
120
No
. o
f p
ati
ents
CPE Pulm c ont Inh PN Ate le c t NP ARDSp CAP ARDSe xp Pu lm F ib r/PE
Fa
ilu
re R
ate
in
%
100
90
80
70
60
50
40
30
20
10
0
CP
E
Th
oracic
trau
ma
Inh
ala
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NIV Failure
Antonelli M. Intensive Care Med 2001;27:1718-28
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ERS Postgraduate Course NIV
Hannover 2009
NIV in transplantation patients
• 40 pts. undergoing solid organ transplantation with acute respiratory failure
• Design: prospective, randomised
• Group A: Standard Therapy
Group B: Standard Therapy + NIPPV
• Primary Endpoint:
Need for Endotracheal Intubation
• Secondary Endpoint: ICU mortality, Length of ICU stay and ventilatory assistance
Antonelli M. JAMA 2000; 283: 235-41
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ERS Postgraduate Course NIV
Hannover 2009
• Evaluation of all 449 patients receiving NPPV for a 1-yr period for acute or acute on chronic respiratory failure – cardiogenic pulmonary edema (n = 97)
– AECOPD (n = 87)
– non-chronic obstructive pulmonary disease acute hypercapnic respiratory failure (n = 35)
– postextubation respiratory failure (n = 95)
– acute hypoxemic respiratory failure (n = 144)
• Intubation rate was 18%, 24%, 38%, 40%, and 60%,
• respectively,
• Hospital mortality for patients with acute hypoxemicrespiratory failure who failed NPPV was 64%.
• Variables associated with NPPV failure – SAPS II (OR 1.07)
– Glasgow Coma Scale (OR, 0.76)
– PaO2/FIO2 ratio (OR, 0.98)
– serum albumin (OR, 0.30)
Schettino G. Crit Care Med 2008; 36:441 –447
NIV – Real Life
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ERS Postgraduate Course NIV
Hannover 2009
Schettino G. Crit Care Med 2008; 36:441 –447
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ERS Postgraduate Course NIV
Hannover 2009
Conditions associated with NIV failure
in acute hypoxemic ARF
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ERS Postgraduate Course NIV
Hannover 2009
NIV in ARDS
• Prospective, multiple-center cohort study
• Three European intensive care units having expertise
• with NPPV
• 147 patients on NPPV
• NPPV improved gas exchange and avoided intubation in 79 patients (54%)
• Avoidance of intubation was associated with – less VAP (2% vs. 20%)
– lower ICU mortality rate (6% vs. 53%)
• Intubation was more likely – in patients who were older
– had a higher SAPS II
– needed a higher level of PEEP and PSV
• SAPS II >34 and a PaO2/FIO2 <175 after 1 hr of NPPV were independently associated with NPPV failure and need for ETI
Antonelli M. Crit Care Med 2007; 35:18 –27
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ERS Postgraduate Course NIV
Hannover 2009
Postextubation ARF
• Randomised, controlled study
• 37 centres, 8 countries
• MV < 48h
• Respiratory Failure in between 48 h after extubation
• NIV – Vt 5ml/kg BW
– Goal: SaO2 > 90%
• Vs. Standardtherapie – O2-Insufflation
– Physiotherapy
Esteban A. NEJM 2004; 350: 2452-60
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ERS Postgraduate Course NIV
Hannover 2009
Postextubation ARF
Esteban A. NEJM 2004; 350: 2452-60
Mortality 25 % (NIV) vs. 14 %
(O2)
RR for death for NIV 1,78 (95% CI 1,03 – 3,20)
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ERS Postgraduate Course NIV
Hannover 2009
• Prospective cross over study
• 10 pts. with acute lung injury
– paO2/FiO2 < 300 mmHg (mean 132, PCO2 41 mmHg)
– SaO2> 92% under NIV
– RRsyst > 90 mmHg
• Objective:
To assess the short term efffects of non invasive ventilation and CPAP
Non invasive Ventilation in ALI
L´Her E. AJRCCM 2005; online August 4
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ERS Postgraduate Course NIV
Hannover 2009
Non invasive Ventilation in ALI
• Prospective cross over study
• 10 pts. with acute lung injury
– paO2/FiO2 < 300 mmHg (mean 132, PCO2 41 mmHg)
– SaO2> 92% under NIV
– RRsyst > 90 mmHg
• Objective:
To assess the short term efffects of non invasive ventilation and CPAP
L´Her E. AJRCCM 2005; online August 4
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ERS Postgraduate Course NIV
Hannover 2009
ARMA trial, 2000
NEJM 342:1301,
ARMA trial - major outcome parameters
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ERS Postgraduate Course NIV
Hannover 2009
ALVEOLI trial, 2004
NEJM 351:327,
ALVEOLI trial - outcome
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ERS Postgraduate Course NIV
Hannover 2009
NIV in ARDS
Antonelli M. Crit Care Med 2007; 35:18 –27
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ERS Postgraduate Course NIV
Hannover 2009
ILA in ARDS
• Retrospective analysis of
extracorporal interventional
lung assist (ILA)
• 90 pts. with ARDS in a
tertiary university center
• Before, 2 and 24 hrs after
implementation
– Improvement in Oxygen
– Normalisation of pCO2
– 73 of 90 pts. survived
– Complication Rate 24.4%
Bein T. CCM 2006: 34: 1372-77
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ERS Postgraduate Course NIV
Hannover 2009
ILA in Postoperative ARDS
• 7 Patients with postoperative ARDS in Barcelona, Spain
– 5 pneumonectomy
– 2 lobectomy
• 29% of CO perfuse ILA
• No Change in Hemodynamics
• Improvement in Respiratory Function
• Decrease in Il-6
• 6 of 7 pts. survived in comparision to 2 of 9 in a historical cohort
Iglesias M. Ann Thorac Surg 2008: 85: 237-44
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