Palliating delirium in patients with cancer

doi:10.1016/S1470-2045(09)70018-X

The Lancet Oncology

Volume 10, Issue 2, February 2009, Pages 164-172

https://doi.org/10.1016/S1470-2045(09)70018-X Get rights and content

Summary

Delirium is a frequent complication in oncology. Its definition as a disorder of consciousness, attention, and cognition is useful to elaborate a rational framework of its pathophysiology and to interpret the role of different aetiological factors and therapeutic interventions. Many aetiologies and an interaction between risk and predisposing factors have been shown to contribute to most cases of delirium. A screening of potential aetiologies is always mandatory to benefit reversible cases. The palliative treatment of symptoms of delirium includes non-pharmacological, environmental, and preventive interventions and the use of haloperidol. If haloperidol fails to control delirium, sedation with other drugs can be necessary. Specific attention to the qualitative aspects of care and to the effect of delirium on family members should be given in the overall assessment of the patient in his or her cancer trajectory.

Introduction

Delirium (figure 1) is one of the most common neurological complications seen in hospitalised patients with cancer.¹ Its frequency in oncology compared with other medically ill populations is shown in table 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11 which highlights how elderly individuals and patients with advanced or terminal cancer are especially at risk from this complication. The probability of developing delirium is determined by the combined effect of predisposing or vulnerability factors, such as previous cognitive failure or dementia and age,4, 12 incident factors, such as drug toxicity and metabolic abnormalities, and other conditions that are more often associated with the severity of the underlying illness (figure 1). Delirium in cancer can be a challenging diagnosis, because it can be a reversible complication, it can herald the progression of the disease to the brain, and it can be irreversible as part of the terminal evolution of an incurable disease.

The aims of this Review are to clarify the definition of delirium, assess the pathophysiological aspects useful for its understanding and rational therapeutic strategy, and investigate specific aspects of its aetiology and management in patients with cancer. The comprehensive description of specific conditions, such as postoperative delirium and alcohol withdrawal syndrome, is not within the scope of this Review.

Section snippets

Diagnostic definition of delirium

Delirium is a brain syndrome only rarely associated with a specific brain lesion. The Diagnostic and Statistical Manual of Mental Disorders IV—Treatment Revision (panel 1) established the most commonly used diagnostic definition of delirium,¹² which highlights a few core concepts—delirium is a disorder of consciousness and attention combined with abnormalities of cognition and perception. Delirium is an acute syndrome as opposed to dementia, and an organic cause affecting the brain is usually

Pathophysiology and aetiology

The pathophysiology of delirium remains to be fully elucidated, but the reticular formation of the brainstem, with its connection with the hypothalamus, thalamus, and diffuse effects on the cortex—regulating normal wakefulness and sleep—is thought to have a significant role. The neurotransmitters and receptors that are important for wakefulness and consciousness functions, and for toxic and pharmacological effects, are listed in panel 3.15, 22, 23, 24 Among the neurotransmitters, a central role

Assessment of cognitive functions

A formal assessment of cognitive function is needed in patients who develop acute mental status changes and would be desirable in routine monitoring of patients who are at an especially high risk of developing delirium. Although there are a plethora of assessment instruments that are potentially useful,²⁴ the most interesting and practically useful are restricted to a few. The Mini-mental State Exam is sensitive to changes in cognition and includes items that explore temporal orientation and

Non-pharmacological interventions

Screening potentially reversible aetiological factors is a mandatory initial step in all cases of delirium. Even in the advanced phase of cancer, 50% of delirium episodes are reversible, especially when associated with drug toxicity.⁹ It is important to remember that providing safety, companionship, orientation, a quiet environment, emotional support to both the patient and the care-givers, and a caring relationship can avoid pharmacological and eventually physical restraint in many patients

Effect of delirium on family and care-givers

Delirium is regarded by family and care-givers as a difficult experience to witness.⁷¹ In one study, high levels of distress were reported by spouses and by the nurses caring for patients with delirium.⁷² In a multicentre Japanese study, 50% of family members reported being emotionally distressed about the experience of terminal delirium.73, 74 The same researchers also identified some aspects of care that were perceived as important in this situation by family members, including: respect for

Conclusion

Delirium is a demanding clinical condition that complicates the history of patients with cancer. Strategies for early detection, prevention, and management are still insufficient. Careful diagnostic assessment and appropriate care should be combined to meet the needs of patients with different clinical perspectives and disease burden. An interdisciplinary approach to the clinical management and research of delirium would enhance our understanding of a syndrome that covers many disciplines of

Search strategy and selection criteria

Articles for this Review were identified by a search of Medline, Current Content, and Pubmed by use of the search terms “delirium”, “cancer”, and “delirium and neoplasm”, and by a hand search of major textbooks and three monographic books on delirium. References from identified articles were selected for relevance, with priority given to systematic reviews and meta-analyses. Only articles published in English between 1990, and 2008, were included, unless necessary to support specific

References (75)

R Hart et al.
Validation of a cognitive test for delirium in medical ICU patients
Psychosomatics
(1996)
PM Fayers et al.
Which Mini-mental State Exam items can be used to screen for delirium and cognitive impairment?
J Pain Symptom Manage
(2005)
W Breitbart et al.
The Memorial Delirium Assessment Scale
J Pain Symptom Manage
(1997)
J Gaudreau et al.
Fast, systematic and continuous delirium assessment in hospitalized patients: the Nursing Delirium Screening Scale
J Pain Symptom Manage
(2005)
J Dalmau et al.
Paraneoplastic syndromes of the CNS
Lancet Neurol
(2008)
F Stiefel et al.
Acute confusional states in patients with advanced cancer
J Pain Symptom Manage
(1992)
W Breitbart et al.
An open trial of olanzapine for the treatment of delirium in hospitalized cancer patients
Psychosomatics
(2002)
M Mirski et al.
Critical care sedation for neuroscience patients
J Neurol Sci
(2007)
N Sykes et al.
The use of opioids and sedatives at the end of life
Lancet Oncol
(2003)
T Morita et al.
Efficacy and safety of palliative sedation therapy: a multicenter, prospective, observational study conducted on specialized palliative care units in Japan
J Pain Symptom Manage
(2005)

T Morita et al.

Ethical validity of palliative sedation therapy: a multicenter, prospective, observational study conducted on specialized palliative care units in Japan

J Pain Symptom Manage

(2005)

W Breitbart et al.

The delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouse/caregivers and nurses

Psychosomatics

(2002)

T Morita et al.

Terminal delirium: recommendations from bereaved families

J Pain Symptom Manage

(2007)

PD Clouston et al.

The spectrum of neurological disease in patients with systemic cancer

Ann Neurol

(1992)

J Francis et al.

A prospective study of delirium in hospitalized elderly

JAMA

(1990)

SE Levkoff et al.

Delirium. The occurrence and persistence of symptoms among elderly hospitalized patients

Arch Intern Med

(1992)

SK Inouye et al.

A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics

Ann Intern Med

(1993)

SK Inouye et al.

Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability

JAMA

(1996)

V Ljubisavjevic et al.

Risk factors for development of delirium among oncology patients

Gen Hosp Psychiatry

(2003)

J Gaudreau et al.

Psychoactive medications and risk of delirium in hospitalized cancer patients

J Clin Oncol

(2005)

H Minagawa et al.

Psychiatric morbidity in terminally ill cancer patients

Cancer

(1996)

PG Lawlor et al.

Occurrence, causes and outcome of delirium in patients with advanced cancer

Arch Intern Med

(2000)

A Caraceni et al.

The impact of delirium on the short-term prognosis of advanced cancer patients

Cancer

(2000)

MJ Massie et al.

Delirium in terminally ill cancer patients

Am J Psychiatry

(1983)

Diagnostic and statistical manual of mental disorders, fourth edition. Text revision. DSM IV–TR

(2000)

A Zeman

Consciousness

Brain

(2001)

JP Giacino

Disorders of consciousness: differential diagnosis and neuropathologic features

Semin Neurol

(1997)

J Posner et al.

Plum and Posner's diagnosis of stupor and coma

(2007)

R Baht et al.

Delirium as a disorder of consciousness

J Neurol Neurosurg Psychiatry

(2007)

DJ Meagher et al.

Phenomenology of delirium. Assessment of 100 adult cases using standardized measures

Br J Psychiatry

(2007)

ZJ Lipowski

Delirium: acute confusional states

(1990)

B Liptzin et al.

An empirical study of delirium subtypes

Br J Psychiatry

(1992)

KR Farrell et al.

Misdiagnosing delirium as depression in medically ill elderly patients

Arch Intern Med

(1995)

PT Trzepacz

Update on the neuropathogenesis of delirium

Dement Geriatr Cogn Disord

(1999)

J Lindesay et al.

Delirium in old age

(2002)

A Caraceni et al.

Delirium: acute confusional states in palliative medicine

(2003)

J Rudolph et al.

The anticholinergic risk scale and anticholinergic adverse effects in older persons

Arch Intern Med

(2008)

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Diagnosis and management of delirium in hospital oncology services
2022, Journal of Geriatric Oncology
Citation Excerpt :
In patients with later-stage terminal illness, it exceeds 85% and, of these, between 10 and 30% require palliative sedation. More than 50% of patients undergoing myeloablative therapy with bone marrow transplantation experience an episode of delirium within four weeks post-transplantation [10]. Risk factors for delirium in patients with cancer have been classified as direct and indirect (Fig. 1).
The diagnosis of delirium in oncologic services is a challenge; nowadays, there is very little evidence-based information available to guide the medical personnel in the diagnosis and decision taking regarding delirium in the oncologic patient.
This article provides an updated review of the literature with extensive information on delirium in patients with cancer; the subject includes its definition, clinical features, precipitating and triggering factors, the frequency of delirium in oncological patients, its consequences, its treatment, and prognosis.
Skilled nursing facility placement in hospitalized elderly patients with colon cancer
2016, European Journal of Surgical Oncology
The current study sought to determine predictive risk factors and inpatient resource utilization associated with discharge to skilled nursing facility (SNF) in hospitalized elderly patients with colon cancer.
Inpatient data from U.S. community hospital discharges from 2003 to 2011 was analyzed in a retrospective cohort study using the Healthcare Cost and Utilization Project, National Inpatient Sample (HCUP-NIS). Subjects included hospitalized postoperative colon cancer patients over age of 65 (N = 98,797).
The proportion of elderly colon cancer patients discharged to a SNF increased by 16.67% from 2003 to 2011 (18–21%). Elderly patients discharged to a SNF had increased hospitalization costs (+$10,293.70, p < 0.01) compared to elderly colon cancer patients discharged home. Hospitalization predictive risk factors associated with SNF placement include age above 75 (OR, 4.07; 95% CI, 3.90, 4.25; p < 0.01), paralysis (OR, 3.60; 95% CI, 3.06–4.23; p < 0.01), length of stay (LOS) 10 days or more (OR, 3.00; 95% CI, 2.88–3.13; p < 0.01), psychoses (OR, 2.91; 95% CI, 2.56–3.32; p < 0.01), and neurological disorders (OR, 2.34; 95% CI, 2.17–2.52; p < 0.01).
Despite increased costs and worse clinical outcomes associated with SNF placement, over 40% increase of hospital discharge to SNF should be anticipated from this population over the next 20 years. Neurologic and psychiatric comorbidities have significantly negative clinical impacts and increase the likelihood of colon cancer patients' discharge to a SNF.
Prevalence of delirium in patients with advanced cancer admitted to a palliative care unit
2016, Medicina Paliativa
Conocer la prevalencia de delirium en los pacientes diagnosticados de enfermedad oncológica avanzada y terminal ingresados en una unidad de cuidados paliativos (UCP). Analizar la prevalencia relacionada con factores sociodemográficos y clínicos.
Estudio observacional descriptivo durante 6 años (2007-2012) de los pacientes diagnosticados de enfermedad oncológica en fase avanzada y terminal ingresados consecutivamente en una UCP. Se recogieron las siguientes variables: diagnóstico de delirium, edad, género, índice de Karnofsky, localización tumoral primaria, extensión de la enfermedad, síntomas (dolor, disnea) y mortalidad.
De los 1.995 pacientes ingresados en la UCP durante los 6 años, 1.826 (91,5%) fueron incluidos en el estudio por presentar enfermedad oncológica. De los 1.826 pacientes, 497 (27,2%) presentaron delirium. La edad media fue de 72,3 ± 11,7 años, el 77,3% presentaron enfermedad metastásica y el 79,9% fallecieron durante el ingreso. La frecuencia del género masculino (66% vs. 61%) y la presencia de dolor (58% vs. 45,9%) fueron significativamente superiores en los pacientes con delirium que en los pacientes sin él. No se hallaron diferencias significativas respecto a la edad media y a la frecuencia de disnea. No hubo diferencias significativas entre los pacientes ≤ 75 años y los > 75 años respecto a la prevalencia de delirium (27,6% vs. 26,8%). Las localizaciones tumorales primarias que presentaron frecuencias más altas de delirium fueron: cerebral (39,3%), hepática (36%), y riñón y vías urinarias (34,5%).
La prevalencia de delirium en los pacientes con cáncer avanzado y terminal ingresados en una UCP fue del 27,2%. La prevalencia no fue mayor en edades avanzadas. El delirium fue significativamente más frecuente en hombres y en pacientes con dolor. Los pacientes con tumor cerebral primario presentaron una mayor frecuencia de delirium.
To determine the prevalence of delirium in patients admitted to a palliative care unit (PCU) diagnosed with advanced cancer disease, and its associated sociodemographic and clinical factors.
An observational study was conducted during a 6-year period (2007-2012) of patients suffering from an advanced cancer disease admitted to a PCU. Variables: delirium diagnosis, age, gender, Karnofsky performance status, primary tumour location, tumour stage, symptoms (pain, dyspnoea), and mortality.
Of the 1,995 patients admitted to PCU in the study period 1,826 patients diagnosed with advanced cancer were included. Of these 1,826 patients, 497 (27.2%) suffered from delirium. The mean age was 72.3 ± 11.7 years, and 77.3% had metastatic disease, and 79.9% died during admission. The frequency of male gender (66% vs. 61%) and the presence of pain (58% vs. 45.9%) were significantly higher in patients with delirium than in patients without delirium. No significant statistically differences in the mean age and the presence of dyspnoea were found. There were no significant differences between patients ≤ 75 years and > 75 years (27.6% vs. 26.8%) for the prevalence of delirium. Within primary tumour locations, the major prevalence of delirium was in brain (39.3%), liver (36%), and kidney-urinary tract (34.5%) tumours.
The prevalence of delirium in advanced cancer patients admitted to a PCU was 27.2%. Prevalence of delirium was not associated with advanced age. Delirium was significantly more prevalent in men, and in patients who suffered from pain. Patients with primary brain tumour had the highest incidence of delirium.
Palliative Care in the Emergency Department
2015, Critical Care Nursing Clinics of North America
Citation Excerpt :
Laboratory tests to consider include (1) complete blood cell count, (2) electrolytes, renal and liver function tests, (3) analysis of urine, (4) arterial blood gas, (5) chest radiograph, (6) electrocardiogram, and (7) appropriate cultures. Additionally, a careful evaluation of the medication administered and the possible interactions and cognitive side effects should be evaluated.44 Pharmacologic and nonpharmacologic interventions also may be used to treat the delirium.
An analytical framework for delirium research in palliative care settings: Integrated epidemiologic, clinician-researcher, and knowledge user perspectives
2014, Journal of Pain and Symptom Management
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If consistent with the agreed goals of care, the standard approach in palliative care is to identify and treat modifiable precipitant factors.17,34–36 As delirium frequently accompanies the terminal phase of illness in palliative care settings, there is a risk that some potentially reversible episodes may be overlooked or prematurely perceived as terminal.3,17 Conversely, there is the risk that overly aggressive medical interventions can be applied in nonreversible episodes of delirium.
Delirium often presents difficult management challenges in the context of goals of care in palliative care settings.
The aim was to formulate an analytical framework for further research on delirium in palliative care settings, prioritize the associated research questions, discuss the inherent methodological challenges associated with relevant studies, and outline the next steps in a program of delirium research.
We combined multidisciplinary input from delirium researchers and knowledge users at an international delirium study planning meeting, relevant literature searches, focused input of epidemiologic expertise, and a meeting participant and coauthor survey to formulate a conceptual research framework and prioritize research questions.
Our proposed framework incorporates three main groups of research questions: the first was predominantly epidemiologic, such as delirium occurrence rates, risk factor evaluation, screening, and diagnosis; the second covers pragmatic management questions; and the third relates to the development of predictive models for delirium outcomes. Based on aggregated survey responses to each research question or domain, the combined modal ratings of “very” or “extremely” important confirmed their priority.
Using an analytical framework to represent the full clinical care pathway of delirium in palliative care settings, we identified multiple knowledge gaps in relation to the occurrence rates, assessment, management, and outcome prediction of delirium in this population. The knowledge synthesis generated from adequately powered, multicenter studies to answer the framework's research questions will inform decision making and policy development regarding delirium detection and management and thus help to achieve better outcomes for patients in palliative care settings.
Treating an established episode of delirium in palliative care: Expert opinion and review of the current evidence base with recommendations for future development
2014, Journal of Pain and Symptom Management
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The most common medications used to effect sedation for refractory delirium at the end of life are methotrimeprazine, chlorpromazine, midazolam, and phenobarbital.129 Methotrimeprazine (levomepromazine), a phenothiazine, is often used in agitated delirium at the end of life, in which its sedative properties and subcutaneous route of administration are advantageous.87,130,131 However, it is not available worldwide including in the United States.
Delirium is a highly prevalent complication in patients in palliative care settings, especially in the end-of-life context.
To review the current evidence base for treating episodes of delirium in palliative care settings and propose a framework for future development.
We combined multidisciplinary input from delirium researchers and other purposely selected stakeholders at an international delirium study planning meeting. This was supplemented by a literature search of multiple databases and relevant reference lists to identify studies regarding therapeutic interventions for delirium.
The context of delirium management in palliative care is highly variable. The standard management of a delirium episode includes the investigation of precipitating and aggravating factors followed by symptomatic treatment with drug therapy. However, the intensity of this management depends on illness trajectory and goals of care in addition to the local availability of both investigative modalities and therapeutic interventions. Pharmacologically, haloperidol remains the practice standard by consensus for symptomatic control. Dosing schedules are derived from expert opinion and various clinical practice guidelines as evidence-based data from palliative care settings are limited. The commonly used pharmacologic interventions for delirium in this population warrant evaluation in clinical trials to examine dosing and titration regimens, different routes of administration, and safety and efficacy compared with placebo.
Delirium treatment is multidimensional and includes the identification of precipitating and aggravating factors. For symptomatic management, haloperidol remains the practice standard. Further high-quality collaborative research investigating the appropriate treatment of this complex syndrome is needed.

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ReviewPalliating delirium in patients with cancer

Summary

Introduction

Section snippets

Diagnostic definition of delirium

Pathophysiology and aetiology

Assessment of cognitive functions

Non-pharmacological interventions

Effect of delirium on family and care-givers

Conclusion

Search strategy and selection criteria

Psychosomatics

J Pain Symptom Manage

J Pain Symptom Manage

J Pain Symptom Manage

Lancet Neurol

J Pain Symptom Manage

Psychosomatics

J Neurol Sci

Lancet Oncol

J Pain Symptom Manage

J Pain Symptom Manage

Psychosomatics

J Pain Symptom Manage

The spectrum of neurological disease in patients with systemic cancer

Ann Neurol

A prospective study of delirium in hospitalized elderly

JAMA

Delirium. The occurrence and persistence of symptoms among elderly hospitalized patients

Arch Intern Med

A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics

Ann Intern Med

Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability

JAMA

Risk factors for development of delirium among oncology patients

Gen Hosp Psychiatry

Psychoactive medications and risk of delirium in hospitalized cancer patients

J Clin Oncol

Psychiatric morbidity in terminally ill cancer patients

Cancer

Occurrence, causes and outcome of delirium in patients with advanced cancer

Arch Intern Med

The impact of delirium on the short-term prognosis of advanced cancer patients

Cancer

Delirium in terminally ill cancer patients

Am J Psychiatry

Diagnostic and statistical manual of mental disorders, fourth edition. Text revision. DSM IV–TR

Consciousness

Brain

Disorders of consciousness: differential diagnosis and neuropathologic features

Semin Neurol

Plum and Posner's diagnosis of stupor and coma

Delirium as a disorder of consciousness

J Neurol Neurosurg Psychiatry

Phenomenology of delirium. Assessment of 100 adult cases using standardized measures

Br J Psychiatry

Delirium: acute confusional states

An empirical study of delirium subtypes

Br J Psychiatry

Misdiagnosing delirium as depression in medically ill elderly patients

Arch Intern Med

Update on the neuropathogenesis of delirium

Dement Geriatr Cogn Disord

Delirium in old age

Delirium: acute confusional states in palliative medicine

The anticholinergic risk scale and anticholinergic adverse effects in older persons

Arch Intern Med

Review
Palliating delirium in patients with cancer