A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease

Am J Respir Crit Care Med. 2017 Apr 1;195(7):871-880. doi: 10.1164/rccm.201601-0083OC.

Abstract

Rationale: During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O2, but its impact on clinical outcomes remains unknown.

Objectives: To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O2 in reducing NIV failure (25-15%) in severe hypercapnic COPD exacerbations.

Methods: This was a prospective, randomized, open-label trial in 16 intensive care units (ICUs) and 6 countries. Inclusion criteria were COPD exacerbations with PaCO2 ≥ 45 mm Hg, pH ≤ 7.35, and at least one of the following: respiratory rate ≥ 25/min, PaO2 ≤ 50 mm Hg, and oxygen saturation (arterial [SaO2] or measured by pulse oximetry [SpO2]) ≤ 90%. A 6-month follow-up was performed.

Measurements and main results: The primary endpoint was NIV failure (intubation or death without intubation in the ICU). The secondary endpoints were physiological parameters, duration of ventilation, duration of ICU and hospital stay, 6-month recurrence, and rehospitalization rates. The trial was stopped prematurely (445 randomized patients) because of a low global failure rate (NIV failure: air/O2 14.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O2 group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, PaCO2, and encephalopathy score improved significantly faster with heliox. ICU stay was comparable between the groups. In patients intubated after NIV failed, patients on heliox had a shorter ventilation duration (7.4 ± 7.6 d vs. 13.6 ± 12.6 d; P = 0.02) and a shorter ICU stay (15.8 ± 10.9 d vs. 26.7 ± 21.0 d; P = 0.01). No difference was observed in ICU and 6-month mortality.

Conclusions: Heliox improves respiratory acidosis, encephalopathy, and the respiratory rate more quickly than air/O2 but does not prevent NIV failure. Overall, the rate of NIV failure was low. Clinical trial registered with www.clinicaltrials.gov (NCT 01155310).

Trial registration: ClinicalTrials.gov NCT01155310.

Keywords: chronic obstructive pulmonary disease; helium; noninvasive ventilation; outcome.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Gas Analysis / statistics & numerical data
  • Female
  • Helium / therapeutic use*
  • Hospitalization / statistics & numerical data
  • Humans
  • Length of Stay / statistics & numerical data
  • Male
  • Noninvasive Ventilation / methods*
  • Oxygen / therapeutic use*
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / therapy*
  • Recurrence
  • Treatment Outcome

Substances

  • Helium
  • heliox
  • Oxygen

Associated data

  • ClinicalTrials.gov/NCT01155310