- Despite its prevalence in palliative care, delirium is underdiagnosed, especially hypoactive delirium. [1-2] A high index of clinical suspicion is needed. Diagnosis is important for management, prognostication, and in order to counsel families. [3-4] The onset of delirium is associated with a worsening prognosis. [4-9]
- Delirium in palliative care patients can be a potentially reversible condition. 
- Delirium is more common in patients with previous cognitive impairment or dementia, which makes identification and assessment more difficult. 
- Delirium is a condition which causes significant distress to patients, families and staff. [4, 12-13] The presence of delirium makes it much harder to assess and treat other problems such as pain or depression. 
- Since delirium symptoms fluctuate, assessment should be part of routine care. Like pain, delirium is most accurately assessed if it is monitored regularly rather than being screened for intermittently. There are a number of validated tools which can be used  including the Confusion Assessment Method (CAM) [15-16] and the Nursing Delirium Screening Scale (NuDESC). 
- There is often more than one predisposing and precipitating factor for delirium in palliative care. 
Delirium is defined as a condition of disturbed consciousness, with reduced ability to focus, sustain or shift attention. The DSM IV - revised diagnostic criteria  for delirium require
- altered cognition or a perceptual disturbance (which is not better accounted for by dementia),
- symptoms develop over hours to days and tend to fluctuate during the course of the day, and
- evidence of an aetiological cause for the delirium.
Delirium may be
- hyperactive (presenting with agitation, hyperarousal, and restlessness), or
- hypoactive (presenting with drowsiness, lethargy and reduced levels of arousal), or
- a mixed pattern in which the symptoms fluctuate between hyperactive and hypoactive. 
Delirium is extremely common in palliative care patients.  It becomes more frequent towards the end of life, and is an independent predictor of mortality. [4,7,20] The diagnosis is often missed, or may be confused with depression or dementia. Hypoactive delirium in particular is under-diagnosed and is the most frequent subtype of delirium in palliative care settings. [1,8]
Delirium may be reversible, although there is evidence that in some patients it can be persistent  and associated with longer term cognitive problems. [5,22] Much of the evidence about prognosis and treatment of delirium comes from the aged care and critical care literature. However the focus of care in these populations may be different from that in palliative care, particularly in very advanced disease.  In palliative care patients delirium is frequently multifactorial, and when the main precipitant is irreversible, or due to other factors (for example patient wishes, risk or burden of the interventions) the decision may be made not to pursue active investigation.
Factors which should be considered as possible contributors to delirium in a palliative care patient, and treated as appropriate, include:
- Metabolic and biochemical disorders (eg, renal failure, hypercalcaemia, hyponatraemia, dehydration, hypoxia, hypercapnia)
- Hepatic encephalopathy
- Structural cerebral disease (eg, primary or secondary cancer, leptomeningeal disease, radiotherapy to the brain)
- Medications (eg, psychoactive medications such as benzodiazepines, opioids, corticosteroids, antidepressants, or medications with an anticholinergic effect)
- Drug withdrawal (eg, alcohol, benzodiazepines, nicotine)
- Environmental (hospital admission and associated procedures, uncorrected sensory deficits eg, vision and hearing).
Terminal restlessness is a cluster of symptoms. Most often described are a combination of agitation and altered mental state, occurring close to the end of life. There is no agreed definition of this condition. Its relationship with delirium, and its management and potential for reversibility are poorly understood. Assessment must include a consideration of alternative diagnoses. The differential diagnosis for this symptom complex may include: poorly controlled physical symptoms such as pain, itch, urinary retention or faecal impaction in a patient who is obtunded; akathisia, myoclonus and other movement disorders; partial complex seizures; paraneoplastic limbic encephalitis; and PTSD or other psychotic disorder. When it causes distress in a dying patient, sedation may be the appropriate goal of treatment, and antipsychotics and benzodiazepines are currently the mainstay of therapy, but these have not been formally evaluated. [4,23]
Related pages on this topic cover:
Pharmacological management of delirium
Non-pharmacological management of delirium.
Active research areas / controversies
- It is unclear whether hyperactive and hypoactive delirium have the same pathophysiology, prognostic significance and responses to treatment. [19,24] The pathophysiology, assessment and management of terminal restlessness has not been well studied.
- Multicomponent intervention studies  modify the environment to prevent or reduce the duration of delirium. Whether this approach is likely to be effective in palliative care settings has not yet been studied. However it is likely that the hospitalised elderly population in which it has shown benefit has similarities with many patients in the palliative setting.
- Placebo-controlled trials are still needed to answer the question of whether and which antipsychotics are effective in the treatment of delirium, which targeted symptoms they impact on, whether they improve delirium resolution, and how they should be titrated. [6,26]
- The possibility of pharmacological prophylaxis has also been identified in non-palliative care populations, however further work is needed to study agents showing promise. [6-7,27] Medications being trialled include antipsychotics, anticholinesterases, melatonin, and prophylactic gabapentin as an opioid sparing agent. [6,28]
- A Cochrane review of the role of benzodiazepines in management of delirium found no evidence to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients.