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– Withdrawn and somnolent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