A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease* Salvatore Maurizio Maggiore; Jean-Christophe M. Richard; Fekri Abroug; Jean Luc Diehl; Massimo Antonelli; Philippe Sauder; Jordi Mancebo; Miquel Ferrer; Franc ¸ ois Lellouche; Laurent Lecourt; Gae ¨ tan Beduneau; Laurent Brochard N oninvasive ventilation (NIV) is a standard treatment for pa- tients with acute exacerbation of chronic obstructive pulmo- nary disease (COPD) (1). NIV improves al- veolar ventilation and reduces the work of breathing (2, 3). Through these physiologic effects, NIV has the potential to reduce morbidity, mortality, and duration of hos- pital stay in patients with hypercapnic re- spiratory failure (2, 4 –7). Nevertheless, NIV has limitations and is not successful in all patients (8, 9). In two surveys, it was shown that the use of this technique as the initial ventilatory approach in acute respiratory failure has increased from 16% to 24% of admissions to the intensive care unit (ICU), with a failure rate of approximately 40% (10, 11). As patient’s comfort and compli- ance are critical to the success of NIV (12), technical improvements could be of great interest (13). Helium-oxygen (HeO 2 ) is a gas mix- ture with a lower density than standard air-oxygen, and its use is associated with decreased resistance to gas flow (14 –16). HeO 2 reduces inspiratory muscle load when airway resistance is high, thus re- ducing dyspnea and improving gas ex- change in patients with severe COPD (17) or severe asthma (18, 19). The use of HeO 2 enhances the unloading effects of NIV. In patients with acute exacerbations of COPD, NIV with HeO 2 reduces dys- pnea, improves CO 2 elimination, and de- creases work of breathing more than con- ventional NIV with air-oxygen (20, 21). Positive results from physiologic studies have generated the hypothesis that NIV with HeO 2 might improve clinical out- come in patients with acute exacerbation of COPD. This hypothesis has been as- sessed in a randomized, controlled trial which compared the effects of NIV with HeO 2 or air-oxygen on intubation rate and other clinical outcomes (22). This trial failed to show a beneficial effect of HeO 2 possibly because of a low intubation rate in the control group and, conse- quently, an insufficient statistical power. Objective: To assess the effect of a helium-oxygen mixture on intubation rate and clinical outcomes during NIV in acute exac- erbation of chronic obstructive pulmonary disease. Design: Multicenter, prospective, randomized, controlled trial. Setting: Seven intensive care units. Patients: A total of 204 patients with known or suspected chronic obstructive pulmonary disease and acute dyspnea, PA CO2 > 45 mmHgand two among the following factors: pH <7.35, PA O2 <50mmHg, respiratory rate >25/min. Interventions: NIV randomly applied with or without helium (inspired oxygen fraction 0.35) via a face mask. Measurements and Main Results: Duration and complications of NIV and mechanical ventilation, endotracheal intubation, dis- charge from intensive care unit and hospital, mortality at day 28, adverse and serious adverse events were recorded. Follow-up lasted until 28 days since enrollment. Intubation rate did not significantly differ between groups (24.5% vs. 30.4% with or without helium, p  0.35). No difference was observed in terms of improvement of arterial blood gases, dyspnea, and respiratory rate between groups. Duration of NIV, length of stay, 28-day mortality, complications and adverse events were similar, al- though serious adverse events tended to be lower with helium (10.8% vs. 19.6%, p  0.08). Conclusions: Despite small trends favoring helium, this study did not show a statistical superiority of using helium during NIV to decrease the intubation rate in acute exacerbation of chronic obstructive pulmonary disease. (Crit Care Med 2010; 38:000 – 000) KEY WORDS: mechanical ventilation; heliox; acute respiratory failure; chronic obstructive pulmonary disease; endotracheal intubation *See also p. xxx. From the Department of Anesthesiology and Inten- sive Care (SMM, MA), Agostino Gemelli University Hos- pital, Universita ` Cattolica del Sacro Cuore, Rome, Italy; Medical Intensive Care Unit (SMM, FL, LB), AP-HP, Henri Mondor Hospital, Cre ´ teil, France; Medical Inten- sive Care Unit (J-CMR, GB), Charles Nicolle University Hospital, Rouen, France; UPRES 38 30 (J-CMR), Rouen, France; Intensive Care Unit (FA), F. Bourguiba University Hospital, Monastir, Tunisia; Medical Inten- sive Care Unit (JLD), Georges Pompidou University Hospital, Paris, France; Medical Intensive Care Unit (PS), Hospices Civiles Hospital, Strasbourg, France; Intensive Care Unit (JM), San Pau University Hospital, Barcelona, Spain; Respiratory Intensive Care Unit (MF), Clinical Institute of Pneumology and Thoracic Surgery, Clinic University Hospital, Barcelona, Spain; Research Department (LL), Air Liquide Sante ´ International, Paris, France; Universite ´ Paris 12 (LB), Cre ´ teil, France; INSERM U 955 (LB), Cre ´ teil, France. This work was supported, in part, by Air Liquide Sante ´ International. Authors SMM and JCMR contributed equally to this work. Dr. Laurent Brochard received grant support from Air Liquide Saute ´ International and has been employed with Air Liquide Saute ´ . The remaining authors have not disclosed any potential conflicts of interest. For information regarding this article, E-mail: laurent.brochard@hmn.aphp.fr Copyright © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e3181b78abe 1 Crit Care Med 2010 Vol. 38, No. 1