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Management of agitation
& delirium “They drive you crazy”
Dr Lesley Young FRCP Senior Clinical Lecturer, NUMed Malaysia &
Consultant Geriatrician, City Hospitals Sunderland, UK
Confusion and agitation in
palliative care
• Definitions
• Why it matters
• Recognising it
• Risks and precipitants
• Why does delirium
happen?
• Managing it
Dementia
Delirium
Deafness
Dysphasia
Not understanding
the question?
CONFUSION
Limbic encephalitis
Disorientation
Terminal
restlessness
DSM IV Disturbance of consciousness
reduced ability to focus, sustain or shift attention
A change in cognition or the development of a perceptual disturbance that is not due to a pre-existing dementia
Develops over a short period of time and tends to fluctuate
Evidence that disturbance is caused by the direct physiological consequences of a general medical condition, substance intoxication or withdrawal.
The get out clause……
Clarifying “confusion”
• Delirium
– Multi-factorial syndrome characterised by
acute onset of cognitive dysfunction,
fluctuating course and deficits in attention
– Most common neuropsychiatric complication
in advanced cancer
• 26-44% admissions to hospice/hospital
• 80% advanced cancer patients experience
terminal delirium in the last few days of life
Why does it matter?
• Results in worsening of quality of life/death
for...
– Patient
– Family
• Interferes with adequate clinical evaluation
• Impedes patient participation in decision
making
And yet....
• Delirium generally under-researched
• Limited research on delirium in palliative
care setting
– Ambiguous terminology
– Failure to use validated diagnostic tools
Moreover.....
• Major reason for admission to palliative
care units
• Failure to recognise / misdiagnosis
– Associated with worse outcomes
AND......
• Up to 50% cases potentially reversible
Manifestations of delirium in
palliative care • Very variable and fluctuating
– Restlessness and Agitation
• Misdiagnosed as pain
– Slow thinking
– Sleep disturbance
– Withdrawn and somnolent
• Misdiagnosed as depression
– Disorientation
– Perceptual disturbances
Types of delirium
Hypoactive
• M
Hypoactive
Mixed
Delirium recognition
1. Recognition of cognitive deficits
– MMSE, AMTS etc
2. Delirium specific screening tools
– Confusion Assessment Method (CAM)
– MDAS • Many others
Confusion Assessment Method (Inouye 1990)
Presence of acute
onset +/- fluctuating
course
Disorganised thinking
Altered level of
consciousness
Inattention
OR Delirium
CONFUSION ASSESSMENT METHOD (CAM)
SHORTENED VERSION WORKSHEET
Patient: Staff: Date:
• BOX 1 • I. ACUTE ONSET AND FLUCTUATING COURSE
• a) Is there evidence of an acute change in mental status from the patient’s baseline? No _Yes___
• b) Did the (abnormal) behaviour fluctuate during the day, that is tend to come and go or increase and decrease in severity? No Yes___
• II. INATTENTION
• Did the patient have difficulty focusing attention, for example, being easily distractible or having difficulty keeping track of what was being said? No_ Yes___
______________________________________________________________________
• BOX 2 • III. DISORGANIZED THINKING
• Was the patient ‘s thinking disorganized or incoherent, such as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject? No Yes_
• IV. ALTERED LEVEL OF CONSCIOUSNESS
• Overall, how would you rate the patient’s level of consciousness?
Alert (normal) or
Vigilant (hyper alert) • __Lethargic (drowsy, easily aroused)
• __Stupor (difficult to arouse)
• __Coma (unrousable)
• Do any checks appear?
• (any level of consciousness other than ‘normal’) No _Yes__
• ________________________________________________________________________
• If all ‘Yes’s’ in Box 1 are checked and at least one ‘Yes’ in Box 2 is checked a diagnosis of delirium is suggested.
• Adapted from Inouye SK et al, Clarifying Confusion: The Confusion Assessment Method. A New Method for Detection of Delirium. Ann Intern Med. 1990; 113:941-8.
MDAS
1. Disorientation (5 place, 5 time)
2. Reduced level of consciousness
3. Short term memory impairment (Recall of 3 words)
4. Impaired digit span
– 3,4, then 5 forwards
– 3, then 4 backwards
5. Reduced ability to maintain and shift attention (during interview)
6. Disorganised thinking (during interview)
7. Perceptual disturbance
8. Delusions
9. Decreased or increased psychomotor activity
10. Sleep-wake cycle disturbance
Scored /30 (>13 predictive of delirium)
Why it matters
Agitated delirium
Overload of team Stress of family
Sedation
After Centeno et al Palliative Care 2004
• Delirium is under-recognised
– Only 20-50% of cases recorded as delirium in
records
– Failure to recognize associated with poor
management (Young, Age and Ageing 2003)
– Use of cognitive screening tests can improve
recognition (Jitapunkul 1991, Anthony Psychol Med 1982, O`Keeffe
JAGS 2005, Young, Age and Ageing 2003)
• Delirium misdiagnosed as.....
– Poorly defined pain (Bruera, Cancer 2009)
– Depression
• Delirium is an independent predictor of
poor prognosis for short term survival (Lawlor,
Arch Int Med 2000)
– 21 days v 39 days (Caraceni, Cancer 2000)
Misdiagnosis of
delirium
Inappropriate
prescribing of
opiates
Worsening of
delirium
Failure to identify
and treat cause
Death
Stress
What causes delirium?
• Multi-factorial
• Precipitating factors v risk factors
Risk factors
Precipitating
factors
Vuln
era
bility
Insult
High
Low Mild
Noxious
After Inouye
What causes delirium?
Risk factors
• Age > 75
• Dementia (2/3 cases)
• Severe illness
• Physical frailty
• Cachexia
Precipitating factors
• Drugs
• Infections
• Metabolic derangements
– Hypoxia
– Hyponatraemia
– Hypercalcaemia
– Dehydration
• Organ failure
Precipitants of delirium prospective study General Medical in-patients >70yrs n=87
J Laurila EDA 2009
• Infections (84%)
• Drugs (46%)
• Metabolic disturbance (47%)
• Circulatory conditions (26%)
• Neurological (24%)
• Other post-op (18%)
=245%!!!
Delirium is multi-factorial
Delirium is multi-factorial
How does it happen • Direct insults to brain
– General and regional energy deprivation (hypoxia,
hypoglycaemia, stroke etc)
– Metabolic (e.g. hyponatraemia, hypercalcaemia..)
– Drugs
– Infection (e.g. meningitis, encephalitis etc)
• Aberrant stress response
– Activation of limbic-hypothalamic-pituitary-adrenal
axis
• Inflammatory theory
– peripheral stimulus causing intracerebral
inflammatory response involving cytokines etc
• ......and lots more theories...
Cholinergic theory
• ↓ Ach → delirium
• Evidence that:
– Severe illness / trauma → ↓ Ach
– Hypoxia/hypoglycaemia →↓ Ach
– Thiamine deficiency →↓ Ach
– ↑Serum Anti Cholinergic Activity in delirium
– Anticholinergic drugs cause delirium
Drug causes of delirium in
palliative care • Opiates
• Anticholinergic drugs
• Benzodiazepines
Opiates
• Opiods implicated in 21-76% cases (Zimmerman,
Am J Hospice Pall Med, 2011)
– Often required for adequate analgesia
– Beware misdiagnosis of delirium for pain
• Consider
– Cessation
– Dose reduction
– Opiod switching
– Adequate hydration
(Leonard, J Psychosomatic Research 2008; Lawlor, Arch Int Med 2000)
Anticholinergic drugs
• Often used in end of life symptom control:
– Scopolamine / hyoscine patches
– Ipratropium
– Urinary anticholinergics
– H1 antagonists e.g. Hydroxyzine
– H2 antagonists e.g. Ranitidine
– Anti-emetics e.g. Promethazine
– Anti-diarrhoeals e.g. Loperamide
• Effects are cumulative
Benzodiazepines
• Frequently used in palliative care
• Often inappropriately prescribed for
agitation (Agar, Pall Med 2008)
– Precipitate or worsen delirium (Breitbart, Am J Psych 1996)
• May be appropriate for terminal delirium in
last few hours.
Management
• Identify and, if appropriate treat cause(s)
• Drug review
• Assess patients priorities
– Maintaining cognitive function
– Patient / staff / carer safety
– Reducing distress
Potentially reversible causes in
palliative care • Infection
– Treat with suitable antibiotic
• Dehydration
– IV or SC fluids
• Raised ICP
– steroids
• Hypercalcaemia
– Bisphosphonates
• Hyponatraemia
– Fluid restriction / demeclocycline
• Hypoxia
– Oxygen therapy
Managing symptoms
• Antipsychotics:
– Limited good research evidence, but
widespread expert opinion
– Haloperidol (best evidence and most experience)
• Low dose, oral/im/iv/sc
• Effective in reducing hallucinations, delusions and
disorganised thinking
• Also effective as an anti-emetic
– Atypical antipsychotics
• Less evidence, no more effective than haloperidol
Other drugs • Methylphenidate hydrochloride
– Trialled in cancer patients with hypoactive delirium
of unidentified cause (Gagnon Rev Psychiatr Neurosci 2005)
• Acetyl cholinesterase inhibitors
– Main stay of treatment for Alzheimer's disease
– Limited research in delirium, mixed conclusions
• Donepezil reduces sedation in opiod-induced sedation –
case series (Slatkin, J Pain Symptom Manag 2001, Bruera, J Pain Symptom Manag
2003)
• Rivastigmine does not decrease duration of delirium in
RCT of ICU patients with delirium and may increase
mortality (Eijk, Lancet 2010)
Terminal delirium
• Symptom management should be targeted
and individualised
– Distressing “Terminal restlessness” not
responding to antipsychotics, may need
benzodiazepines
Non-pharmacological
management
Prevention is better than cure
• HELP
– A targeted multi-component intervention that
can prevent up to 40% incident delirium (in
general hospital populations) (Inouye NEJM 1999)
• Early attention to and avoidance of
precipitants in those at risk.
HELP interventions Cognitive impairment Reality orientation
Therapeutic activities
Vision/hearing impairment Vision/hearing aids
Adaptive equipment
Immobilisation Early mobilisation
Minimising immobilising equipment
Psychoactive medication use Non-pharmacological approaches to sleep/anxiety
Restricted use of sleeping tablets
Dehydration Early recognition
Volume repletion
Sleep deprivation Noise reduction strategies
Sleep enhancement program
HELP
Intervention
Control p Reference
Cognitive decline 8% 26% <0.05 Inouye JAGS 2000
Physical decline 14%
45%
33%
56%
<0.05
0.03
Inouye JAGS 2000
Vidan JAGS 2009
Reduced incident delirium
OR=0.60
RR↓ 35%
6%
OR= 0.4
38%
0.02
0.002
0.03
0.005
Inouye NEJM 1999
Rubin JAGS 2006
Caplan Int Med J 2007
Vidan JAGS 2009
Costs ↓$831
↓$1.25
million/yr
↓$121,425
Rizzo Med care 2001
Rubin JAGS 2006
Caplan Int Med J 2007
LOS ↓0.3 d/pt Rubin JAGS 2006
Falls /1000 pt days 3.8
1.2
11.4
4.7
Inouye NEJM 2009
Non-pharmacological
management
• Communication
– Carers and family
– Team
• Environment
– Avoid restraint
– Familiar objects
– Lighting
– Space to wander & sit
• Access to clock / calendar
• Reality orientation
Identify patients at risk
Implement preventive strategy (HELP)
Recognise delirium
Identify and treat cause(s)
Drug review
Infections
Manage symptoms
Non-pharmacological Pharmacological
Haloperidol
Consider benzodiazepines only
for terminal restlessness in last few hours
Delirium
Everybody's
problem