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