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Intensive Care Med Exp. 2015 December; 3(Suppl 1): A422.
Published online 2015 October 1. doi:  10.1186/2197-425X-3-S1-A422
PMCID: PMC4798073

An international phase iii randomised trial on the efficacy of helium/oxygen during spontaneous breathing and intermittent non-invasive ventilation for severe exacerbations of chronic obstructive pulmonary disease (the E.C.H.O.ICUtrial)


Due to its reduced density, Helium/Oxygen (He/O2) reduces the work of breathing, intrinsic PEEP and hypercapnia more than Air/O2 during non-invasive ventilation (NIV) in COPD exacerbations [1, 2]. Two prospective, randomized multicenter trials were inconclusive in showing a benefit of He/O2 NIV on outcome (intubation, mortality, length of stay (LOS) in ICU) but were potentially underpowered [3, 4].


To evaluate whether 72-hr continuous He/O2 during both spontaneous breathing and NIV is superior to Air/O2 in reducing NIV failure (intubation or mortality during ICU stay) in severe hypercapnic COPD exacerbations. Secondary outcomes included physiological parameters, duration of ventilation, ICU and hospital LOS, 6-month recurrence and rehospitalization rates.


Prospective, randomized multicenter (16 centers in 6 countries) trial, comparing the two gas mixtures for a maximum of 72 hours. Hypothesis was that He/O2 would reduce intubation rate from 25% to 15%, resulting in a total sample size of 670 patients. Spontaneous breathing and NIV were applied with specific devices for He/O2. Same ventilator was used in both arms.


The trial was stopped prematurely for futility (low intubation rate reported by the adjudication committee). 445 patients were included (mean ± SD 68 ± 11 yrs; M:F 69:31%; BMI 26 ± 6 kg/m2; SAPS 3 49 ± 8; Resp rate (RR) 29 ± 6/min - PaO2 75 ± 36 mmHg; PaCO2 69 ± 16 mmHg; pH 7.30 ± 0.06 - intention-to-treat data set), with no baseline difference between He/O2 vs. Air/O2. The primary outcome was negative (Figure (Figure1)1) and baseline pH was the only significant predictor of NIV failure. NIV failure occurred in the first 72 hours (while receiving the study treatment) in 58% of failures with He/O2 and 84% with Air/O2 (p = 0.97). RR (Figure (Figure2),2), pH, PaCO2 and encephalopathy improved faster and with greater magnitude with He/O2

figure 40635_2015_Article_566_Fig1_HTML
Figure 1
figure 40635_2015_Article_566_Fig2_HTML
Figure 2


NIV failure rate was not reduced by He/O2 administered during NIV and spontaneous breathing for up to 72 hrs. Failure rate was low in both groups, reflecting the current efficacy of NIV in decompensated COPD. However, He/O2 led to improved physiological response, thus confirming previous results, and a shorter duration of invasive ventilation and ICU stay in patients with NIV failure.

Grant Acknowledgment Identifier: NCT01155310. Study funded by Air Liquide Healthcare.


1. Jaber S, Fodil R, Carlucci A, Boussarsar M, Pigeot J, Lemaire F, et al. Noninvasive ventilation with helium-oxygen in acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161:1191–1200. doi: 10.1164/ajrccm.161.4.9904065. [PubMed] [Cross Ref]
2. Jolliet P, Tassaux D, Thouret JM, Chevrolet JC. Beneficial effects of helium:oxygen versus air:oxygen noninvasive pressure support in patients with decompensated chronic obstructive pulmonary disease. Crit Care Med. 1999;27(11):2422–2429. doi: 10.1097/00003246-199911000-00017. [PubMed] [Cross Ref]
3. Jolliet P, Tassaux D, Roeseler J, Burdet L, Broccard A, D'Hoore W, et al. Helium-oxygen versus air-oxygen noninvasive pressure support in decompensated chronic obstructive disease: A prospective, multicenter study. Crit Care Med. 2003;31(3):878–884. doi: 10.1097/01.CCM.0000055369.37620.EE. [PubMed] [Cross Ref]
4. Maggiore SM, Richard JC, Abroug F, Diehl JL, Antonelli M, Sauder P, et al. A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease. Crit Care Med. 2010;38(1):145–151. doi: 10.1097/CCM.0b013e3181b78abe. [PubMed] [Cross Ref]

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