title: A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease.
abstract: 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.
  
  
  
  To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O2in reducing NIV failure (25-15%) in severe hypercapnic COPD exacerbations.
  
  
  
  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.
  
  
  
  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/O214.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O2group 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.
  
  
  
  Heliox improves respiratory acidosis, encephalopathy, and the respiratory rate more quickly than air/O2but does not prevent NIV failure. Overall, the rate of NIV failure was low. Clinical trial registered with www.clinicaltrials.gov (NCT 01155310).
authors.affiliation: 1 Intensive Care and Burn Unit, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Jolliet
authors.affiliation: 2 Fattouma Bourguiba University Hospital, Monastir, Tunisia.
authors.forename: Lamia
authors.initials: L
authors.lastname: Ouanes-Besbes
authors.affiliation: 2 Fattouma Bourguiba University Hospital, Monastir, Tunisia.
authors.forename: Fekri
authors.initials: F
authors.lastname: Abroug
authors.affiliation: 3 Abderrahmen Mami Hospital, Ariana, Tunisia.
authors.forename: Jalila
authors.initials: J
authors.lastname: Ben Khelil
authors.affiliation: 3 Abderrahmen Mami Hospital, Ariana, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Besbes
authors.affiliation: 4 Sainte Musse Hospital, Toulon, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Garnero
authors.affiliation: 4 Sainte Musse Hospital, Toulon, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Arnal
authors.affiliation: 5 Cochin Hospital, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Daviaud
authors.affiliation: 5 Cochin Hospital, Paris, France.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Chiche
authors.affiliation: 6 Georges Pompidou European Hospital, Paris, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Lortat-Jacob
authors.affiliation: 6 Georges Pompidou European Hospital, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Diehl
authors.affiliation: 7 Angers University Hospital, Angers, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lerolle
authors.affiliation: 7 Angers University Hospital, Angers, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Mercat
authors.affiliation: 8 Henri-Mondor Hospital, Créteil, France.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Razazi
authors.affiliation: 8 Henri-Mondor Hospital, Créteil, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Brun-Buisson
authors.affiliation: 9 Institut national de la santé et de la recherche médicale, UMR 955, Université Paris Est, Créteil, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durand-Zaleski
authors.affiliation: 5 Cochin Hospital, Paris, France.|10 Air Liquide Santé International, Medical R&D, Jouy-en-Josas, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Texereau
authors.affiliation: 9 Institut national de la santé et de la recherche médicale, UMR 955, Université Paris Est, Créteil, France.|11 University Hospital of Geneva, Intensive Care Unit, Geneva, Switzerland.|12 Li Ka Shing Institute and Keenan Research Centre, St Michael's Hospital, Toronto, Ontario, Canada; and.|13 University of Toronto, Interdepartmental Division of Critical Care Medicine, Toronto, Ontario, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brochard
mesh_terms: D000368:Aged; D001784:Blood Gas Analysis / Q000706:statistics & numerical data; D005260:Female; D006371:Helium / Q000627:therapeutic use*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D063087:Noninvasive Ventilation / Q000379:methods*; D010100:Oxygen / Q000627:therapeutic use*; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology / Q000628:therapy*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D006371:Helium; C038949:heliox; D010100:Oxygen
keywords: chronic obstructive pulmonary disease; helium; noninvasive ventilation; outcome