22ème Journée d’Actualités en Ventilation Artificielle
Fabbri et al. ERJ 2007
Ce
58
140
Pr
59
141
Nd
60
144
Pm
61
145
Sm
62
150
Eu
63
152
Gd
64
157
Tb
65
159
Dy
66
163
Ho
67
165
Er
68
167
Tm
69
169
Yb
70
173
Lu
71
175
Th
90
232
Pa
91
231
U
92
238
Np
93
237
Pu
94
242
Am
95
243
Cm
96
247
Bk
97
249
Cf
98
251
Es
99
254
Fm
100
253
Md
101
256
No
102
254
Lw
103
257
Nb
41
93
Mo
42
96
Tc
43
99
Ru
44
101
Rh
45
103
Pd
46
106
Ag
47
108
Cd
48
112
In
49
115
Sn
50
119
Sb
51
122
Te
52
128
I
53
127
Xe
54
131
Cs
55
133
Ba
56
137
La
57
139
Hf
72
178
Ta
73
181
W
74
184
Re
75
186
Os
76
190
Ir
77
192
Pt
78
195
Au
79
197
Hg
80
201
H
1
1
He
2
4
Li
3
7
Be
4
9
B
5
11
C
6
12
N
7
14
O
8
16
F
9
19
Ne
10
20
Na
11
23
Mg
12
24
Al
13
27
Si
14
28
P
15
31
S
16
32
Cl
17
35
Ar
18
40
K
19
39
Ca
20
40
Sc
21
45
Ti
22
48
V
23
51
Cr
24
52
Mn
25
55
Fe
26
56
Co
27
59
Ni
28
59
Cu
29
64
Zn
30
65
Ga
31
70
Ge
32
73
As
33
75
Se
34
79
Br
35
80
Kr
36
84
Rb
37
85
Sr
38
88
Y
39
89
Zr
40
91
Tl
81
204
Pb
82
207
Bi
83
209
Po
84
210
At
85
210
Rn
86
222
Fr
87
223
Ra
88
226
Ac
89
227
Unq
104
261
Unp
105
262
Unh
106
263
1A
2A
3B 4B 5B 6B 7B 8B 1B 2B
3A 4A 5A 6A 7A
8A
1
2
3
4
5
6
7
He Helium
2
4.0026
Incolore, inodore, insipide, inerte
THE USE OF HELIUM IN THE TREATMENT OF
ASTHMA AND OBSTRUCTIVE LESIONS IN THE LARYNX AND TRACHEA
By ALVAN BARACH, M.D., F.A.C.P., New York,
N.Y.
Ann Int Med 1935; 9: 739-765
Velocity profiles in long straight tubes with axisymmetrical flow
laminar
turbulent
Helium-oxygen makes flow more laminar
The effects are attenuated as FiO2 is increased
The Reynolds number is decreased by 3.6 with an 80:20% He-O2 mixture
He/O2 post-extubation Jaber et al., Am J Respir Crit Care Med 2001; 164: 633-637
18 patients (ø COPD), VM > 48 h, post-extubation
He/O2 lors d'asthme aigu sévère
Manthous et al., Am J Respir Crit Care Med 1995; 151: 310-314
27 pts en respiration spontanée
Jolliet P et al ICM 2003
COPD
under
Mechanical
Ventilation
0
-20
-40
-60
-80
*
* *
0
-20
-40
-60
-80
*
*
* WOB DPdi
NIV + helium-O2 = external + internal Assistance
Noninvasive Ventilation with Helium–Oxygen in Acute Exacerbations of Chronic
Obstructive Pulmonary Disease. Jaber,….Brochard. AJRCCM 2000; 161: 1191
VS-HeO2 VNI-HeO2 VNI-AirO2 VS-HeO2 VNI-HeO2 VNI-AirO2
Crit Care Med 2003; 31: 878-
884
n = 123
Air/O2
He/O2
CCM 2003
Patients' ICU course and outcome Jolliet et al., Crit Care Med 2003; 31: 878-884
Maggiore et al., Crit Care Med 2010; 38: 145-151
Air-O2
HeO2
n=23
n=18
n=7
n=2
≥ 4
NIV duration (days)
ET
I (%
)
0
10
20
30
40
50
60
70
80
0 - 4
p=0.045Air-O2
HeO2
n=23
n=18
n=7
n=2
≥ 4
NIV duration (days)
ET
I (%
)
0
10
20
30
40
50
60
70
80
0 - 4
p=0.045Air-O2
HeO2
Air-O2
HeO2
n=23
n=18
n=7
n=2
≥ 4
NIV duration (days)
ET
I (%
)
0
10
20
30
40
50
60
70
80
0 - 4
p=0.045
n=23
n=18
n=7
n=2
≥ 4
NIV duration (days)
ET
I (%
)
0
10
20
30
40
50
60
70
80
0
10
20
30
40
50
60
70
80
0 - 4
p=0.045p=0.045
Maggiore S, Richard JC et al ICM 2009
OR (fixed)
95% CI
Weight
%
31.5
68.5
100
OR (fixed)
95% CI
0.62 (0.24 – 1.61)
0.61 (0.32 – 1.16)
0.61 (0.35 – 1.04)
HeO2
n/N
8/59
20/96
155
28
Air-O2
n/N
13/64
30/99
163
43
Study
Jolliet (21)
Maggiore
Total
Total events
0.1 0.2 0.5 21 5 10
Favours HeO2 Favours Air-O2
OR (fixed)
95% CI
Weight
%
31.5
68.5
100
OR (fixed)
95% CI
0.62 (0.24 – 1.61)
0.61 (0.32 – 1.16)
0.61 (0.35 – 1.04)
HeO2
n/N
8/59
20/96
155
28
Air-O2
n/N
13/64
30/99
163
43
Study
Jolliet (21)
Maggiore
Total
Total events
0.1 0.2 0.5 21 5 10
OR (fixed)
95% CI
Weight
%
31.5
68.5
100
OR (fixed)
95% CI
0.62 (0.24 – 1.61)
0.61 (0.32 – 1.16)
0.61 (0.35 – 1.04)
Weight
%
31.5
68.5
100
OR (fixed)
95% CI
0.62 (0.24 – 1.61)
0.61 (0.32 – 1.16)
0.61 (0.35 – 1.04)
HeO2
n/N
8/59
20/96
155
28
Air-O2
n/N
13/64
30/99
163
43
Study
Jolliet (21)
Maggiore
Total
Total events
HeO2
n/N
8/59
20/96
155
28
Air-O2
n/N
13/64
30/99
163
43
Study
Jolliet (21)
Maggiore
Total
Total events
0.1 0.2 0.5 21 5 100.1 0.2 0.5 21 5 100.1 0.2 0.5 21 5 100.2 0.5 21 5 10
Favours HeO2 Favours Air-O2Favours HeO2 Favours Air-O2
P= 0.07
From Maggiore S, Richard JC M et al ICM 2009
NIV + helium-O2 = external + internal Assistance
ECHOICU: A multicenter randomized trial
assessing the efficacy of Helium/Oxygen
in severe exacerbations of COPD
P. Jolliet, L. Besbes, F. Abroug, J. Ben Kheli, M. Besbes, JM. Arnal, JD. Chiche, F. Daviaud, JL. Diehl,
B. Lortat-Jacob, A. Mercat, N. Lerolle, K. Razazi, C. Brun-Buisson, S. Bertini A. Corrado,
I. Durand-Zaleski, J. Texereau, L. Brochard
on behalf of the ECHOICU investigators
ClinicalTrials.gov Identifier: NCT01155310
The E.C.H.O.ICU study was sponsored by Air Liquide
HealthCare
Introduction
Due to its reduced density, Helium/O2 (He/O2) reduces
the work of breathing, intrinsic PEEP and hypercapnia
more than Air/O2 during spontaneous breathing1,2 and
non-invasive ventilation (NIV)2,3
1. Am Rev Respir Dis 1960;81:823-829
2. Am J Respir Crit Care Med 2000;161:1191-1200
3. Crit Care Med 1999;27:2422-2429
Two prospective, randomized multicenter trials were
inconclusive in showing a benefit of He/O2 NIV on
outcome (intubation, mortality, length of stay in ICU1,2)
Intubation rate %
Air/O2 He/O2
1.Crit Care Med 2003;31:878-874 20 13
2.Crit Care Med 2010;38:145-151 30.4 24.5
Introduction (2)
Study objective
To determine whether continuously administered He/O2
(during NIV and in-between NIV sessions) for 72 hours
was superior to Air/O2 in reducing NIV failure in COPD
patients with severe hypercapnic exacerbation.
Study end-points
Primary end-point
NIV failure, defined as endotracheal intubation or death
without intubation
Secondary end-points
• Physiological parameters
• Duration of ventilation
• ICU and hospital LOS
• 6-month follow-up (recurrence & rehospitalization)
• Medico-economic analysis
Methods Patients
COPD (known or clinically suspected) requiring NIV for acute
hypercapnic respiratory failure.
NIV criteria
Uncompensated respiratory acidosis (PaCO2 ≥ 45 mmHg and
pHa ≤ 7.35)
and at least one of the following:
- Respiratory rate ≥ 25 b/min
- PaO2 ≤ 50 mmHg
- SaO2 or SpO2 ≤ 90%
Methods (2) He/O2 delivery (up to 3 days)
He/O2 gas cylinders
Sentry He/O2
blenders
HiOx mask Hamilton G5
with He/O2
module
FlexiFit
Facemask
Spontaneous breathing
NIV
Study sample size estimation
• Based on a reduction in the NIV failure rate
from 25% to 15%
• Total 670 patients
• Inclusions stopped prematurely due to low event rate
(adjudication committee) / futility rule
• Total of 445 patients included
Results
He/O2 (n=225) Air/O2 (n=220)
Age (years) 68.9 11.4 66.9 11.4
Gender (M/W) – n 149 / 76 158 / 62
BMI Kg/m2 25.7 5.5 25.9 6.3
Current smokers, n (%) 85 (38%) 94 (43%)
Lung function
Available PFTs, n (%)
FEV1, %predicted value
124 (55%)
36 14
107 (49%)
35 15
Admission in ICU in the last 12 months, n (%) 35 (16%) 27 (12%)
Main provenance
Emergency room – n (%)
Medical ward – n (%)
Home – n (%)
174 (77.3%)
23 (10.2%)
22 (9.8%)
168 (76.4%)
30 (13.6%)
16 (7.3%)
SAPS III (0-217) 49.7 7.9 48.8 7.6
Main causes of COPD exacerbation
Infection – n (%)
Undetermined – n (%)
Cardiac – n (%)
113 (50.2%)
55 (24.4%)
35 (15.6%)
115 (52.3%)
53 (24.1%)
30 (13.6%)
Patient characteristics
Respiratory rate n/min.
pH SpO2
PaCO2 mmHg
Physiological data during first 72 hours
p <0.0001 - all time points
p <0.0001 - all time points
mean ± 95% CI
mean ± 95% CI mean ± 95% CI
mean ± SD
Encephalopathy score over first 72 hrs
mean ± 95% CI
ITT total population He/O2 (n=225) Air/O2 (n=220) p
NIV failure
Intubation, n (%)
NIV duration, days
Length of stay, days
ICU
Hospital
Mortality, n (%)
ICU
Hospital
6-m
33 (14.7%)
31 (13.8%)
5.3 4.2
8.7 6.7
16.2 11.6
12 (5.3%)
8 (3.6%)
20 (8.9%)
32 (14.5%)
32 (14.5%)
5.1 4.6
10.2 11.6
17.0 15.6
15 (6.8%)
3 (1.4%)
17 (7.7%)
0.97
0.82
0.69
0.29
0.74
Main outcomes
0
5
10
15
20
25
30
Cumulative invasive MV duration (ITT)
*Student’s t-test
*p=0.02
days
He/O2
(n=31) Air/O2
(n=32)
log-rank p=0.01
NIV failure subgroup
Air/O2
26.720.9 days
He/O2
15.710.8 days %patie
nts
in IC
U
Duration of index ICU stay
%
pH
90
141 179
35
n = 445
pH was the only predictor of NIV failure (p<0001)
NIV failure rate (%): pH at baseline
Conclusion
• Largest study to date on severe hypercapnic COPD
decompensation requiring NIV + 6 mo. follow-up.
• Largest study on the medical use of He/O2 and first to
assess its continuous administration for 72 h with
specific delivery devices.
Conclusion (2)
• The study confirmed the beneficial physiological
effects and safety of He/O2.
• No reduction in NIV failure rate, but overall intubation
very low.
• Significant reduction in duration of invasive MV and
ICU LOS in patients in whom NIV failed.
Many Thanks to…
Air Liquide medical R&D
H. Taupin M. Labart L. Monnier H. Pasche Les Loges en Josas, France
Endpoint Validation & Safety Committee
Prof E. Vicaut (Chairman) (methodologist, Paris)
Prof S. Nava (intensivist, Bologna)
Prof J. Mancebo (intensivist, Barcelona)
Belgium J. ROESELER Bruxelles
P. BULPA Yvoire
France
C. BRUN-BUISSON Créteil
JM. ARNAL Toulon
P. WOLTER Nice
JD. CHICHE Paris / Cochin
JL. DIEHL Paris /
Pompidou
F. VARGAS Bordeaux
JM. CONSTANTIN Clermont
-Ferrand
P. KALFON Chartres
A. MERCAT Angers
Italy A. CORRADO Florence
Switzerland D. TASSAUX /
L. BROCHARD
Genève
Tunisia F. ABROUG Monastir
M. BESBES Ariana
UK R. HARRISON Stockton
The 16 ECHOICU Investigational teams