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

During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O, 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/O in 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 Pa ≥ 45 mm Hg, pH ≤ 7.35, and at least one of the following: respiratory rate ≥ 25/min, Pa ≤ 50 mm Hg, and oxygen saturation (arterial [Sa] or measured by pulse oximetry [Sp]) ≤ 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/O 14.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, Pa, 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/O but does not prevent NIV failure. Overall, the rate of NIV failure was low. Clinical trial registered with www.clinicaltrials.gov (NCT 01155310).