Chronic obstructive pulmonary disease (COPD) remains associated with substantial morbidity and mortality and has become a leading reason for hospitalization in the United States.1,2 These acute exacerbations of COPD (AECOPDs) may progress to respiratory failure, necessitating mechanical ventilation (MV).3 In fact, approximately 10% of patients with AECOPDs require MV.4 Over the last decade, multiple studies of novel therapies for stable COPD suggest that these treatments help to prevent AECOPDs.5,6 However, there is a paucity of interventions for the management of AECOPDs. Available treatments for AECOPDs include antibiotics, bronchodilators, noninvasive ventilation, and corticosteroids,7 but, unfortunately, nearly all studies of ACEOPDs have excluded persons who are at the highest risk for failure, ie, those who are critically ill. Often patients with impending respiratory failure are excluded from clinical trials because of concerns about safety or because of more practical issues. A critically ill patient is less likely to tolerate an adverse event. Alternatively, it is difficult to determine whether outcomes in patients who are enrolled in the intensive care unit (ICU) are driven by their underlying physiology or by the treatment under study. Similarly, the process of obtaining consent is cumbersome and adds to the challenge of enrolling those in the ICU. Therefore, few researchers venture into the ICU for clinical trials. As a consequence, intensivists are often left extrapolating data from non–critically ill patients. However, is it appropriate to administer medical therapy to patients in the ICU when the safety and efficacy of the therapy has not been demonstrated in this population?