Emergency Department-Initiated Buprenorphine for Opioid Use Disorder: A Randomized Clinical Trial.

Terminal restlessness is loosely defined as intractable restless or agitated behavior without a clear etiology occurring at the end of life, usually in the 5–7 days before death (,). This behavioral phenomenon is commonly recognized in clinical hospice and palliative settings, with estimates that it affects between 25% to 85% of actively dying patients (,). Prior research suggests several predisposing and precipitating factors for terminal restlessness, including frailty, sensory impairment, neoplastic brain disease, renal failure, and exposure to opioids, steroids, or anticholinergics (,). Such symptoms often persist until death and are accompanied by multidimensional distress—physical, emotional, and spiritual distress—as well as heightened motor activity (). Both patients and their care partners (i.e., family or other caregivers) can be profoundly impacted by terminal restlessness (). Family members who witness these severe end-of-life symptoms report significant emotional turmoil, and the agitation associated with terminal restlessness can cause distress for patients, families, and clinicians alike (,). Multiple terms—terminal restlessness, terminal agitation, and terminal delirium—are often used interchangeably in the literature and practice (). There is also a current lack of universally accepted standards for identification, assessment, and treatment of this condition (). In clinical practice, differentiating terminal restlessness from other conditions such as delirium, dementia, “near death awareness”, or reversible conditions such as urinary retention, infection or medication side effect is important (). The distinction carries clinical significance: labeling agitated behavior as “terminal restlessness” often leads to more liberal use of antipsychotics, benzodiazepines, and opioids to relieve suffering—an approach that can escalate to palliative sedation in refractory cases (). Palliative (or “terminal”) sedation, while sometimes necessary to control severe agitation at end of life, remains an ethically disputed practice when used broadly (). Thus, there is a critical balance between improving comfort and avoiding inappropriate sedation. Conceptually, it remains unclear whether terminal restlessness is best understood as a distinct syndrome or simply a manifestation of delirium in the final stage of life (–). Some experts consider terminal restlessness to be essentially an agitated delirium at end of life, particularly in patients with cognitive impairment (). Others debate whether it is a consistent feature of the active dying period (). Major knowledge gaps have been identified in prior work including: (a) the lack of a standardized assessment tool for consistently identifying and measuring terminal restlessness; (b) the need to differentiate general restlessness or other agitation from true terminal restlessness; and (c) the lack of consensus on optimal treatment options ().