Many patients die in a state of delirium—a waxing and waning in level of consciousness and a change in cognition that develops over a short time and is manifested by misinterpretations, illusions, hallucinations, sleep-wake cycle disruptions, psychomotor disturbances (eg, lethargy, restlessness), and mood disturbances (eg, fear, anxiety). Delirium may be hyperactive, hypoactive, or mixed. Hypoactive delirium may be difficult to distinguish from active dying. Agitated delirium at the end of life has been called terminal restlessness.
Some delirious patients may appear “pleasantly confused,” although it is difficult to know what patients experience. In the absence of obvious distress in the patient, a decision by the patient’s family and the clinician not to treat delirium may be considered. More commonly, however, agitated delirium at the end of life is distressing to patients and family and requires treatment. Delirium may interfere with the family’s ability to interact with the patient and may prevent a patient from being able to recognize and report important symptoms. Common reversible causes of delirium include urinary retention, constipation, anticholinergic medications, and pain; these should be addressed whenever possible. There is no evidence that dehydration causes or that hydration relieves delirium. Careful attention to patient safety and nonpharmacologic strategies to help the patient remain oriented (clock, calendar, familiar environment, reassurance and redirection from caregivers) may be sufficient to prevent or manage mild delirium. A randomized trial of placebo compared to risperidone or haloperidol in delirious patients demonstrated increased mortality with neuroleptics. Thus, neuroleptic agents (eg, haloperidol, 1–10 mg orally, subcutaneously, intramuscularly, or intravenously twice or three times a day, or risperidone, 1–3 mg orally twice a day) generally should be avoided. Ramelteon, a melatonin agonist, at 8 mg/day orally has been shown to prevent delirium in seriously ill, older hospitalized patients. It should be avoided in patients with severe liver disease. When delirium is refractory to other treatments and remains intolerable, especially at the end of life, neuroleptic agents or frank sedation may be required to provide relief. Although benzodiazepines can worsen delirium and generally should be avoided, they may be helpful in achieving sedation near the end of life. For example, sedation may be achieved with midazolam (0.5–5 mg/h subcutaneously or intravenously) or barbiturates.