Inclusion Criteria:  Age ≥18 years Patient receiving any NIV modality for acute respiratory failure of any etiology Admitted to ICU, PACU, step-down unit (surgical or medical), or emergency department  Presence of one or more of the following after optimized NIV treatment  Agitation (Defined as a Richmond Agitation and Sedation Scale [RASS] score of ≥+2 or a Riker Sedation-Agitation Scale [SAS] score of ≥5) Patient expresses intolerance or requests removal of NIV secondary to self-reported discomfort, anxiety, or claustrophobia Other reason that the physician feels the patient is intolerant of NIV or agitated, not captured above (all reasons will be recorded)  Exclusion Criteria:  Absence of a functioning pacemaker with one of the following: a-Persistent bradycardia defined as a heart rate (HR) ≤50bpm; b-Second or third-degree heart block; or c- Tachybrady syndrome Persistent hypotension, defined as a mean arterial pressure (MAP) ≤60mmHg despite volume resuscitation and vasopressors Acute hepatic failure Known allergy to dexmedetomidine Pregnancy Acute withdrawal from drugs or alcohol Patients with post-extubation respiratory failure Imminent need for endotracheal intubation Death is deemed imminent and inevitable Patient's goals of care do not include intubation and IMV Patients already on dexmedetomidine at time of enrollment Previously enrolled in the inDEX trial Treating physician refuses enrollment (reasons for refusal will be captured)