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

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/O-2, 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/O-2 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 Pa-CO2 >= 45 mm Hg, pH <= 7.35, and at least one of the following: respiratory rate >= 25/min, Pa-O2 <= 50 mm Hg, and oxygen saturation (arterial [Sa(O2)] or measured by pulse oximetry [Sp(O2)]) <= 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/O-2 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-2 group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, Pa-CO2, 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/O-2 but does not prevent NIV failure. Overall, the rate of NIV failure was low.