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Background
Delirium is defined as a condition of disturbed consciousness, with reduced ability to focus, sustain or shift attention. The DSM IV diagnostic criteria [1] for delirium require altered cognition or a perceptual disturbance (which is not due to dementia), that the symptoms develop over hours to days and tend to fluctuate during the course of the day, and that there is evidence of an aetiological cause for the delirium. Delirium may be either 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. [2] Delirium is often reversible, although there is evidence that in some patients it may be associated with longer term cognitive problems. [3]

Delirium is extremely common in palliative care patients. [4] It becomes more frequent towards the end of life, and is associated with a worsening prognosis. [5] The diagnosis is often missed, or may be confused with depression or dementia. Hypoactive delirium in particular is under-diagnosed. [6] Nonetheless the importance of making the diagnosis is that delirium is a potentially treatable problem, and one which causes serious distress to patients and their families.

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 is different from that in palliative care, particularly in very advanced disease. [7] In palliative care patients delirium is frequently multifactorial. The underlying precipitant, though reversible in many instances, may be irreversible in advanced disease, or due to other factors the decision may be made not to pursue active investigation or intervention.

Terminal restlessness is a cluster of symptoms, most often described as agitation and altered mental state, which occurs 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. When it causes distress in a dying patient sedation may be the goal of treatment, and antipsychotics and benzodiazepines are currently the mainstay of therapy, but these have not been formally evaluated. [7, 8]

Factors which should be considered as possible contributers to delirium in a palliative care patient, and treated as appropriate, include:

• Infection
• 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, steroids, antidepressants, or medications with an anticholinergic effect)
• Drug withdrawal (eg, alcohol, benzodiazepine, nicotine)
• Environmental (hospital admission, uncorrected sensory deficits eg vision and hearing)

This topic will cover:

• Pharmacological management of delirium 
• Non-pharmacological management of delirium.

Key messages

• Despite its prevalence in palliative care, delirium as a distinct problem is underdiagnosed, especially hypoactive delirium. [6] A high index of clinical suspician is needed. Diagnosis is important for managemetn, prognostication, and in order to counsel families. [9]
• Delirium in palliative care patients is a potentially reversible condition. The factors most associated with delirium reversibility are psychoactive medications and dehydration. [4]
• Delirium is more common in patients with previous cognitive impairment or dementia, which makes identification and assessment more difficult. [10]
• Delirium is a condition which causes significant distress to patients and families. [11]
• The presence of delirium makes it much harder to assess and treat other problems such as pain or depression.
• There are a number of validated tools which can be used to screen for delirium in palliative care settings, [12] including the Confusion Assessment Method [13] and the Nursing Delirium Screening Scale. [14] Since delirium symptoms fluctuate, assessment for delirium should be part of routine care. Like pain, delirium is most accurately assessed if it is monitored regularly rather than being screening for intermittently.

Active research areas / controversies

• It is unclear whether hyperactive and hypoactive delirium have the same prognostic significance and responses to treatment [15]. The assessment and management of refractory hyperactive delirium in dying patients (“terminal restlessness”) has not been well studied.
• Whether findings of multicomponent intervention studies [16] which modify the environment to prevent or reduce the duration of delirium can be applied in palliative care settings has not been studied.
• Placebo controlled trials are still needed to answer the question of whether and which antipsychotics are effective in the treatment of delirium, and how they should be titrated. [17]  The possibility of pharmacological prophylaxis has also been identified in non-palliative care populations as an area for future research. [18, 19]
• A Cochrane review of the role of benzodiazepines in management of delirium is under way. [20]
• Studies exploring the attitudes and prescribing practices of Australian palliative care clinicians in relation to management of delirium are under way at present, in order to identify barriers to providing best practice care. [21]

References

1. American Psychiatric Association. DSM-IV, Diagnostic and Statistical Manual of Mental Disorders. 4th ed.  Washington: APA; 1994.
2. de Rooij SE, Schuurmans SJ, van der Mast RC, Levi M. Clinical subtypes of delirium and their relevance for daily clinical practice: a systematic review. International Journal of Geriatric Psychiatry. 2005 Jul;20(5):609-15.  
3. Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychology Review. 2004 Jun;14(2):87-98.  
4. Lawlor PG, Gagnon B, Mancini IL, Pereira JL, Hanson J, Suarez-Almazor ME et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study. Archives of Internal Medicine. 2000 Mar 27;160(6):786-94.  
5. Maltoni M, Caraceni A, Brunelli C, Broeckaert B, Christakis N, Eychmueller S, et al. Prognostic factors in advanced cancer patients: evidence-based clinical recommendations--a study by the Steering Committee of the European Association for Palliative Care. Journal of Clinical Oncology. 2005 Sep 1;23(25):6240-8.  
6. Spiller JA, Keen JC. Hypoactive delirium: assessing the extent of the problem for inpatient specialist palliative care. Palliative Medicine. 2006 Jan;20(1):17-23.  
7. Leonard M, Agar M, Mason C, Lawlor P. Delirium issues in palliative care settings. J Psychosom Res. 2008 Sep;65(3):289-98.
8. Kehl K. Treatment of terminal restlessness: a review of the evidence. Journal of Pain & Palliative Care Pharmacotherapy.  2004;18(1):5-30.  
9. Schuurmans MJ, Duursma SA, Shortridge-Baggett LM. Early recognition of delirium: review of the literature. J Clin Nurs. 2001 Nov;10(6):721-9
10. Fick DM, Agostini JV, Inouye SK. Delirium superimposed on dementia: a systematic review.  Journal of the American Geriatrics Society. 2002 Oct;50(10):1723-32. 
11. Breitbart W, Gibson C, Tremblay A. The delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/caregivers, and their nurses. Psychosomatics. 2002 May-Jun;43(3):183-94.  
12. Hjermstad MJ, Loge JH, Kaasa S. Methods for assessment of cognitive failure and delirium in palliative care patients: implications for practice and research. Palliative Medicine. 2004 Sep;18(6):494-506.  
13. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI.Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Annals of Internal Medicine. 1990 Dec 15;113(12):941-8.  
14. Gaudreau JD, Gagnon P, Harel F, Tremblay A, Roy MA. Fast, systematic, and continuous delirium assessment in hospitalized patients: the nursing delirium screening scale. Journal of Pain and Symptom Management. 2005 Apr;29(4):368-75. 
15. Meagher DJ, O’Hanlon D, O’Mahony E, Casey PR, Trzepacz PT.  Relationship between symptoms and motoric subtype of delirium. Journal of Neuropsychiatry and Clinical Neurosciences. 2000  Winter;12(1):51-6. 
16. Inouye SK, Bogardus ST Jr, Charpentier JA, Leo-Summers L, Acampora D, Holford TR, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. New England Journal of Medicine. 1999 Mar 4;340(9):669-76. 
17. Seitz DP, Gill SS, van Zyl LT. Antipsychotics in the treatment of delirium: a systematic review. Journal of Clinical Psychiatry. 2007 Jan;68(1):11-21. 
18. Bourne RS, Tahir TA, Borthwick M, Sampson EL. Drug treatment of delirium: past, present and future.J Psychosom Res. 2008 Sep;65(3):273-82.
19. Gagnon PR.Treatment of delirium in supportive and palliative care.Curr Opin Support Palliat Care. 2008 Mar;2(1):60-6.
20. Lonergan E, Luxenberg J, Areosa Sastre A, Wyller T. Benzodiazepines for delirium. Cochrane Database of Systematic Reviews. 2007 Apr 18;(2):CD006379. 
21. Agar M, Currow D, Plummer J, Chye R, Draper B. Differing management of people with advanced cancer and delirium by four sub-specialties. Palliative Medicine. 2008 Jul;22(5):633-40. 

This page was created on 15 August 2008 and is due for review in August 2010
Last updated 30 September 2008