Data mainly from hospitalized but also long-term care and emergency department patients suggest that selective or targeted screening based on delirium risk factors or risk score is also an approach worth evaluating [2,7,56–58], though few data exist in relation to predictive models of delirium in the supportive and palliative care population. Despite demonstrable delirium prevention benefits in many other settings , a single evaluation study in palliative care with substantive methodological limitations showed no benefit . Studies are needed to rigorously evaluate the benefits and potential harms of screening in relation to multiple outcomes such as medical intervention requirements, preventive strategies, delirium reversibility, care needs and economic burden [24▪].
There remains a lack of good randomized controlled trial (RCT) evidence for the optimal treatment of delirium in palliative care patients. Furthermore, limited up-to-date clinical practice guidelines on delirium in this patient population are currently available [61▪]. Consequently, management is largely guided by expert opinion [62▪]. A survey of international delirium specialists, predominantly geriatricians and internal medicine physicians from Europe, demonstrated an ongoing lack of consensus as to the management of both hyperactive and hypoactive delirium and the frequency of using antipsychotic medications [63▪]. Haloperidol was the most frequently used antipsychotic for situations in which respondents used pharmacological approaches [63▪]. A pharmacovigilance study of haloperidol in 119 hospice/palliative care patients with delirium reported an average haloperidol dose of 2.1 mg every 24 h in a mostly elderly population with a poor performance status . Over one-third of patients had a reduction in delirium as measured by the Common Toxicity Criteria for Adverse Events (CTCAE)  delirium scale after 48 h of treatment. After 10 days of treatment, somnolence was reported in 11 patients and urinary retention in six patients.
A recently published prospective double-blind RCT compared haloperidol with quetiapine in the management of multifactorial delirium in 52 medically ill hospital inpatients, aged 30–75 years (mean age 56.8 years and 67% male) in Thailand [66▪]. Both antipsychotics were administered with a flexible oral dose scheduled at bedtime and then every 2–3 h as needed for agitation, up to a set maximum dose per 24 h. Benzodiazepines and other antipsychotic medications were not allowed during the study period and there was no placebo arm. Thirteen out of 24 (54.2%) patients completed 7 days of treatment with quetiapine as compared with 22 of 28 (78.6%) patients who received haloperidol. Results were analyzed on an intention-to-treat basis. Mean doses of antipsychotic used were low: quetiapine 67.6 mg/day and haloperidol 0.8 mg/day. The response rates as measured by the reduction in the DRS-R-98 severity scores were not significantly different between the two groups. The total sleep time per day was greater in the quetiapine group, but was not significantly higher than the haloperidol group.
In a prospective observational study of 2453 general hospital inpatients in Japan, the three most common antipsychotics prescribed by consultation-liaison psychiatrists were risperidone (34%), quetiapine (32%) and intravenous haloperidol (20%) for those patients who were unable to take oral antipsychotic . Mean patient age was 73.5 years and the comorbid dementia rate was 30%. Delirium resolved within 1 week in 54% of patients. The rate of serious adverse events was reported as 0.9% with no deaths attributed to antipsychotics. However, electrocardiogram monitoring was not reported. In the study by Hatta et al. and another observational study of 80 patients referred to the consultation-liaison psychiatry service in a tertiary level hospital, it was the psychiatrist who determined the choice of antipsychotic.
Rather than relying on consensus expert opinion, the revised clinical practice guidelines for the management of pain, agitation and delirium in adult intensive patients assigned ‘no recommendation’ to statements if there was insufficient evidence or if, after reviewing the literature, the group could not reach consensus [35▪,36▪]. For adult ICU patients, the task force found low-level evidence for atypical antipsychotics and reduction in delirium duration but no evidence for haloperidol treatment and reduced duration of delirium [35▪]. Whereas some published delirium guidelines have suggested doses of antipsychotics, a less prescriptive approach may increase acceptance and uptake of a guideline into clinical practice, with local guideline adaptation specifically tailored for the local culture and environment.
In the elderly, it has been recommended that medications are reserved for severely agitated patients, or those with severe psychotic symptoms, and low antipsychotic starting doses have been suggested for this population, for example haloperidol 0.25–0.5 mg orally twice a day [8▪▪].
The role of nonpharmacological strategies in both the prevention and treatment of delirium in many medical ill populations, including elderly and postoperative patients, has been demonstrated [8▪▪]. These strategies have been recommended in the recent National Institute for Health and Clinical Excellence clinical practice guidelines, which exclude patients at the end of life [80,81]. This is in contrast with palliative care populations and older people in long-term institutional care wherein nonpharmacological strategies have yet to demonstrate efficacy in delirium prevention [60,82]. Deprescribing (the dose reduction, withdrawal, or cessation) of psychoactive medications is an essential step in management in all patient populations , although for patients with advanced cancer, its benefits have not been clearly demonstrated at this time .
As each specialty (e.g. geriatrics, intensive care and palliative care) has a differing patient population, ongoing evidence and consensus should be sought for both the pharmacological and nonpharmacological management of delirium within each patient group. This can then be systematically evaluated for both efficacy, as assessed by delirium severity rating scales that have been validated in that specific population, and adverse effects using standardized tools specific to each particular patient population.
In a small mixed-methods pilot study of 10 patients receiving palliative sedation or with an agitated delirium, the RASS-PAL (RASS modified for palliative care inpatients) also showed good psychometric properties and high inter-rater reliability . The inter-rater intraclass correlation coefficient range of the RASS-PAL for the five assessment time points was 0.84–0.98. Training in the appropriate use of these instruments is essential, especially for nonexperienced staff [92,93].
Papers of particular interest, published within the annual period of review, have been highlighted as:
1▪. Hosie A, Davidson PM, Agar M, et al. Delirium
prevalence, incidence, and implications for screening
in specialist palliative care
inpatient settings: a systematic review. Palliat Med 2013; 27:486–498.
This is a systematic review of delirium that demonstrates its high occurrence rates in palliative care.
2. Ahmed S, Leurent B, Sampson EL. Risk factors for incident delirium
among older people in acute hospital medical units: a systematic review and meta-analysis. Age Ageing 2014; 43:326–333.
3. Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology 2013; 80:1778–1783.
4. Jacqmin-Gadda H, Alperovitch A, Montlahuc C, et al. 20-Year prevalence projections for dementia and impact of preventive policy about risk factors. Eur J Epidemiol 2013; 28:493–502.
6. Mandelblatt JS, Hurria A, McDonald BC, et al. Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know? Semin Oncol 2013; 40:709–725.
7. Kobayashi D, Takahashi O, Arioka H, et al. A prediction rule for the development of delirium
among patients in medical wards: Chi-Square Automatic Interaction Detector (CHAID) Decision Tree Analysis Model. Am J Geriatr Psychiatry 2013; 21:957–962.
8▪▪. Inouye SK, Westendorp RG, Saczynski JS. Delirium
in elderly people. Lancet 2014; 383:911–922.
This is a comprehensive, rigorous, state-of-the-art review.
9▪. Leonard M, Nekolaichuk C, Meagher D, et al. Practical assessment
in palliative care
. J Pain Symptom Manage 2014; [Epub ahead of print].
This is a comprehensive review of assessment tools with practical recommendations for use in palliative care settings.
10▪. American Psychiatric AssociationDiagnostic and statistical manual of mental disorders: DSM-5. 5th ed2013; Arlington, VA:American Psychiatric Association,
These are long-awaited consensus-derived, gold standard diagnostic criteria.
11. World Health Organisation. ICD-10 Classifications of Mental and Behavioural Disorder: Clinical Descriptions and Diagnostic Guidelines. 1992.
12. Laurila JV, Pitkala KH, Strandberg TE, Tilvis RS. Impact of different diagnostic criteria on prognosis of delirium
: a prospective study. Dement Geriatr Cogn Disord 2004; 18:240–244.
13. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the confusion assessment
method. A new method for detection of delirium
. Ann Intern Med 1990; 113:941–948.
14▪. Leonard M, Agar M, Spiller J, et al. Delirium
diagnostic and classification challenges in palliative care
: subsyndromal delirium
, comorbid delirium
-dementia and psychomotor subtypes. J Pain Symptom Manage 2014; (In Press).
This is a rigorous review that addresses major diagnostic challenges in palliative care settings.
15▪. Cole MG, Ciampi A, Belzile E, Dubuc-Sarrasin M. Subsyndromal delirium
in older people: a systematic review of frequency, risk factors, course and outcomes. Int J Geriatr Psychiatry 2013; 28:771–780.
This is a systematic review that highlights the importance of and controversies surrounding subsyndromal delirium.
16. Trzepacz PT, Mittal D, Torres R, et al. Validation of the Delirium
Rating Scale-revised-98: comparison with the delirium
rating scale and the cognitive test for delirium
. J Neuropsychiatry Clin Neurosci 2001; 13:229–242.
17. Ryan DJ, O’Regan NA, Caoimh RO, et al. Delirium
in an adult acute hospital population: predictors, prevalence and detection. BMJ Open 2013; 3: 10.1136/bmjopen-2012-001772
18. Franco JG, Trzepacz PT, Meagher DJ, et al. Three core domains of delirium
validated using exploratory and confirmatory factor analyses. Psychosomatics 2013; 54:227–238.
19. Whittamore KH, Goldberg SE, Gladman JR, et al. The diagnosis, prevalence and outcome of delirium
in a cohort of older people with mental health problems on general hospital wards. Int J Geriatr Psychiatry 2014; 29:32–40.
20▪. Barron EA, Holmes J. Delirium
within the emergency care setting, occurrence and detection: a systematic review. Emerg Med J 2013; 30:263–268.
This is a systematic review of delirium in a setting wherein the frequency of missed diagnosis is particularly high.
21. Doran DM, Hirdes JP, Blais R, et al. Adverse events among Ontario home care clients associated with emergency room visit or hospitalization: a retrospective cohort study. BMC Health Serv Res 2013; 13:227.
22▪. Hey J, Hosker C, Ward J, et al. Delirium
in palliative care
: detection, documentation and management
in three settings. Palliat Support Care 2013; [Epub ahead of print].
Although this is a retrospective study, it is well structured and provides useful discussion. It demonstrates the poor level of delirium documentation and recognition in palliative care settings.
23. Downing LJ, Caprio TV, Lyness JM. Geriatric psychiatry review: differential diagnosis and treatment of the 3 D's - delirium
, dementia, and depression. Curr Psychiatry Rep 2013; 15:365.
24▪. Lawlor PG, Davis DHJ, Ansari M, et al. An analytic framework for delirium
research in palliative care
settings: integrated epidemiological, clinician-researcher and knowledge user perspectives. J Pain Symptom Manage 2014; [Epub ahead of print].
This is an open-access article that summarizes the input of multiple researchers, generates a series of pertinent research questions that arise along the care pathway for a patient in a palliative care setting and reports on survey findings in an effort to prioritize the research questions.
25▪. Hosie A, Agar M, Lobb E, et al. Palliative care
nurses’ recognition and assessment
of patients with delirium
symptoms: a qualitative study using critical incident technique. Int J Nurs Stud 2014; [Epub ahead of print].
Clearly presented qualitative study that examines the critical issues relating to nurses recognition of delirium.
26▪. Hosie A, Lobb E, Agar M, et al. Identifying the barriers and enablers to palliative care
nurses’ recognition and assessment
symptoms: a qualitative study. J Pain Symptom Manage 2014; [Epub ahead of print].
This is another well presented qualitative study that identified both barriers and enablers in relation to nurses recognition of delirium.
27. Kennelly SP, Morley D, Coughlan T, et al. Knowledge, skills and attitudes of doctors towards assessing cognition in older patients in the emergency department. Postgrad Med J 2013; 89:137–141.
28. Kaneko M, Ryu S, Nishida H, et al. Nurses’ recognition of the mental state of cancer patients and their own stress management
- a study of Japanese cancer-care nurses. Psychooncology 2013; 22:1624–1629.
29▪. O’Hanlon S, O’Regan N, Maclullich AM, et al. Improving delirium
care through early intervention: from bench to bedside to boardroom, Journal of Neurology. Neurosurg Psychiatry 2014; 85:207–213.
This is a review that focuses on early recognition, addresses health policy needs regarding delirium and provides a useful 12-point plan for improved delirium care.
30. Saczynski JS, Kosar CM, Xu G, et al. A tale of two methods: chart and interview methods for identifying delirium
. J Am Geriatr Soc 2014; 62:518–524.
31▪. Kerr CW, Donnelly JP, Wright ST, et al. Progression of delirium
in advanced illness: a multivariate model of caregiver and clinician perspectives. J Palliat Med 2013; 16:768–773.
This study provides detailed and useful insights from family caregivers regarding the prodromal phase of delirium development.
32▪. Brummel NE, Vasilevskis EE, Han JH, et al. Implementing delirium screening
in the ICU: secrets to success. Crit Care Med 2013; 41:2196–2208.
This study provides useful implementation strategies for delirium screening derived from the ICU experience.
33. Rice KL, Castex J. Strategies to improve delirium
recognition in hospitalized older adults. J Contin Educ Nurs 2013; 44:55–56.
34▪. Yanamadala M, Wieland D, Heflin MT. Educational interventions to improve recognition of delirium
: a systematic review. J Am Geriatr Soc 2013; 61:1983–1993.
This is a systematic review highlighting educational initiatives to promote knowledge and skill but also the importance of leadership engagement, and use of clinical pathways and assessment tools.
35▪. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management
of pain, agitation, and delirium
in adult patients in the intensive care unit. Crit Care Med 2013; 41:263–306.
These are the comprehensive, rigorously developed guidelines that could serve as a model for guideline development in other settings.
36▪. Barr J, Kishman CP Jr, Jaeschke R. The methodological approach used to develop the 2013 Pain, Agitation, and Delirium
Clinical Practice Guidelines for adult ICU patients. Crit Care Med 2013; 41 (9 Suppl 1):S1–S15.
This article describes the rigorous approach used in the development of guidelines for delirium management in intensive care.
37. Carrothers KM, Barr J, Spurlock B, et al. Contextual issues influencing implementation and outcomes associated with an integrated approach to managing pain, agitation, and delirium
in adult ICUs. Crit Care Med 2013; 41 (9 Suppl 1):S128–S135.
38. Katzman R, Brown T, Fuld P, et al. Validation of a short Orientation-Memory-Concentration Test of cognitive impairment. Am J Psychiatry 1983; 140:734–739.
39. Gaudreau JD, Gagnon P, Harel F, et al. Fast, systematic, and continuous delirium assessment
in hospitalized patients: the nursing delirium screening
scale. J Pain Symptom Manage 2005; 29:368–375.
40. Breitbart W, Rosenfeld B, Roth A, et al. The Memorial Delirium Assessment
Scale. J Pain Symptom Manage 1997; 13:128–137.
41. Yang FM, Jones RN, Inouye SK, et al. Selecting optimal screening
items for delirium
: an application of item response theory. BMC Med Res Methodol 2013; 13:8.
42. Fadul N, Kaur G, Zhang T, et al. Evaluation of the memorial delirium assessment
scale (MDAS) for the screening
by means of simulated cases by palliative care
health professionals. Support Care Cancer 2007; 15:1271–1276.
43▪. Shi Q, Warren L, Saposnik G, Macdermid JC. Confusion assessment
method: a systematic review and meta-analysis of diagnostic accuracy. Neuropsychiatr Dis Treat 2013; 9:1359–1370.
This is a systematic review of the most commonly used assessment tool in delirium screening.
44. Han JH, Wilson A, Vasilevskis EE, et al. Diagnosing delirium
in older emergency department patients: validity and reliability of the delirium
triage screen and the brief confusion assessment
method. Ann Emerg Med 2013; 62:457–465.
45. Steis MR, Evans L, Hirschman KB, et al. Screening
using family caregivers: convergent validity of the Family Confusion Assessment
Method and interviewer-rated Confusion Assessment
Method. J Am Geriatr Soc 2012; 60:2121–2126.
46. Sands MB, Dantoc BP, Hartshorn A, et al. Single Question in Delirium
(SQiD): testing its efficacy against psychiatrist interview, the Confusion Assessment
Method and the Memorial Delirium Assessment
Scale. Palliat Med 2010; 24:561–565.
47. Lingehall HC, Smulter N, Engstrom KG, et al. Validation of the Swedish version of the Nursing Delirium Screening
Scale used in patients 70 years and older undergoing cardiac surgery. J Clin Nurs 2013; 22:2858–2866.
48. Neufeld KJ, Leoutsakos JS, Sieber FE, et al. Evaluation of two delirium screening
tools for detecting postoperative delirium
in the elderly. Br J Anaesth 2013; 111:612–618.
49. de la Cruz M, Noguera A, San Miguel-Arregui MT, et al. Delirium
, agitation, and symptom distress within the final seven days of life among cancer patients receiving hospice care. Palliat Support Care 2014; 20:1–6.
50▪. Bellelli G, Morandi A, Davis DH, et al. Validation of the 4AT, a new instrument for rapid delirium screening
: a study in 234 hospitalised older people. Age Ageing 2014.
Validation of a new, extremely brief screening tool with high sensitivity (89.7%).
51▪. O’Regan NA, Ryan DJ, Boland E, et al. Attention! A good bedside test for delirium
? J Neurol Neurosurg Psychiatry 2014; [Epub ahead of print].
This article highlights the value of ‘months of the year backwards’ test as a brief test of attention.
52. Detroyer E, Clement PM, Baeten N, et al. Detection of delirium
in palliative care
unit patients: A prospective descriptive study of the Delirium
Scale administered by bedside nurses. Palliat Med 2014; 28:79–86.
53▪. Tieges Z, McGrath A, Hall RJ, Maclullich AM. Abnormal level of arousal as a predictor of delirium
and inattention: an exploratory study. Am J Geriatr Psychiatry 2013; 21:1244–1253.
Describes the use of an observational scale to rate level of arousal. This is a brief, minimally burdensome tool that might be studied further in palliative and supportive care settings.
54. Ryan K, Leonard M, Guerin S, et al. Validation of the confusion assessment
method in the palliative care
setting. Palliat Med 2009; 23:40–45.
55. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166:1338–1344.
56. Carrasco MP, Villarroel L, Andrade M, et al. Development and validation of a delirium
predictive score in older people. Age Ageing 2014; 43:346–351.
57. Cole MG, McCusker J, Voyer P, et al. Symptoms of delirium
predict incident delirium
in older long-term care residents. Int Psychogeriatr 2013; 25:887–894.
58. Kennedy M, Enander RA, Tadiri SP, et al. Delirium
risk prediction, healthcare use and mortality of elderly adults in the emergency department. J Am Geriatr Soc 2014; 62:462–469.
59. Reston JT, Schoelles KM. In-facility delirium
prevention programs as a patient safety strategy: a systematic review. Ann Intern Med 2013; 158 (5 Pt 2):375–380.
60. Gagnon P, Allard P, Gagnon B, et al. Delirium
prevention in terminal cancer: assessment
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61▪. Bush SH, Bruera E, Lawlor PG, et al. Clinical practice guidelines for delirium management
: potential application in palliative care
. J Pain Symptom Manage 2014; [Epub ahead of print].
This article highlights the need for formal evaluation of implemented delirium guidelines in palliative care populations, and also for more robust research evidence to inform their content.
62▪. Bush SH, Kanji S, Pereira JL, et al. Treating an established episode of delirium
in palliative care
: expert opinion and review of the current evidence base with recommendations for future development. J Pain Symptom Manage 2014; [Epub ahead of print].
This article describes expert consensus opinion and research agenda from an international multidisciplinary delirium study planning meeting.
63▪. Morandi A, Davis D, Taylor JK, et al. Consensus and variations in opinions on delirium
care: a survey of European delirium
specialists. Int Psychogeriatr 2013; 25:2067–2075.
This is a survey of international delirium specialists that not only reveals similarities but also many differences in approaches to delirium management.
64. Crawford GB, Agar MM, Quinn SJ, et al. Pharmacovigilance in hospice/palliative care
: net effect of haloperidol for delirium
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66▪. Maneeton B, Maneeton N, Srisurapanont M, Chittawatanarat K. Quetiapine versus haloperidol in the treatment of delirium
: a double-blinded, randomized, controlled trial. Drug Des Devel Ther 2013; 7:657–667.
This double-blinded RCT using low doses of either quetiapine or haloperidol in 52 medically ill hospitalized patients reported similar response and remission rates between groups.
67. Hatta K, Kishi Y, Wada K, et al. Antipsychotics for delirium
in the general hospital setting in consecutive 2453 inpatients: a prospective observational study. Int J Geriatr Psychiatry 2014; 29:253–262.
68. Yoon HJ, Park KM, Choi WJ, et al. Efficacy and safety of haloperidol versus atypical antipsychotic medications in the treatment of delirium
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69▪. Candy B, Jackson KC, Jones L, et al. Drug therapy for delirium
in terminally ill adult patients. Cochrane Database Syst Rev 2012; 11:004770.
Published online in November 2012, this intervention review updated the previous Cochrane review by Jackson and Lipman in 2004. Candy's review found no new prospective trials meeting the inclusion criteria since the 2004 review. The authors concluded that insufficient evidence exists for drug therapy in delirium management in this population.
70▪. Meagher DJ, McLoughlin L, Leonard M, et al. What do we really know about the treatment of delirium
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pharmacotherapy. Am J Geriatr Psychiatry 2013; 21:1223–1238.
This is a thought-provoking article that concludes although evidence is limited, there is tentative support for antipsychotics in the treatment of delirium. The article includes excellent summary tables of pharmacological studies of antipsychotics in the treatment of delirium across patient populations, including palliative care, and provides Jadad scores for comparison studies.
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73▪. Maldonado JR. Neuropathogenesis of delirium
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This is an extremely comprehensive and detailed review, which summarizes seven theories that are currently proposed for the pathogenesis of delirium.
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83. Thompson W, Farrell B. Deprescribing: what is it and what does the evidence tell us? Can J Hosp Pharm 2013; 66:201–202.
84. Lindsay J, Dooley M, Martin J, et al. Reducing potentially inappropriate medications in palliative cancer patients: evidence to support deprescribing approaches. Support Care Cancer 2014; 22:1113–1119.
85. Bruera E, Hui D, Dalal S, et al. Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial. J Clin Oncol 2013; 31:111–118.
86. Nakajima N, Hata Y, Kusumuto K. A clinical study on the influence of hydration volume on the signs of terminally ill cancer patients with abdominal malignancies. J Palliat Med 2013; 16:185–189.
87. de Graeff A, Dean M. Palliative sedation therapy in the last weeks of life: a literature review and recommendations for standards. J Palliat Med 2007; 10:67–85.
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91▪. Brinkkemper T, van Norel AM, Szadek KM, et al. The use of observational scales to monitor symptom control and depth of sedation in patients requiring palliative sedation: a systematic review. Palliat Med 2013; 27:54–67.
Highlights that the few studies reporting the use of observational monitoring tools for palliative sedation, as determined by their systematic review, were of limited quality and identified current gaps for future research.
92. Benitez-Rosario MA, Castillo-Padros M, Garrido-Bernet B, et al. Members of the Asocacion Canaria de Cuidados Paliativos (CANPAL) Research Network. Appropriateness and reliability testing of the modified Richmond Agitation-Sedation Scale in Spanish patients with advanced cancer. J Pain Symptom Manage 2013; 45:1112–1119.
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