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

Dysphasia

Delirium

CONFUSION
Limbic encephalitis

Terminal restlessness

Deafness

Not understanding the question?

Disorientation

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Slow thinking Sleep disturbance Withdrawn and somnolent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)

Disorganised thinking Presence of acute onset +/- fluctuating course OR

Delirium

Inattention Altered level of consciousness

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 patients baseline? b) Did the (abnormal) behaviour fluctuate during the day, that is tend to come and go or increase and decrease in severity? No _Yes___ 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 patients 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) ________________________________________________________________________ If all Yess in Box 1 are checked and at least one Yes in Box 2 is checked a diagnosis of delirium is suggested.

No _Yes__

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. 2. 3. 4. Disorientation (5 place, 5 time) Reduced level of consciousness Short term memory impairment (Recall of 3 words) 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

Stress of family

Overload of team

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

Stress
Failure to identify and treat cause
Worsening of delirium

Death

What causes delirium?

Multi-factorial Precipitating factors v risk factors
Risk factors
Precipitating factors Noxious

High
Vulnerability

Low

Mild

Insult
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 Drugs Metabolic disturbance Circulatory conditions Neurological Other post-op

(84%) (46%) (47%) (26%) (24%) (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 Vision/hearing impairment Reality orientation Therapeutic activities Vision/hearing aids Adaptive equipment

Immobilisation
Psychoactive medication use

Early mobilisation Minimising immobilising equipment

Non-pharmacological approaches to sleep/anxiety Restricted use of sleeping tablets Early recognition Volume repletion Noise reduction strategies Sleep enhancement program

Dehydration Sleep deprivation

HELP Intervention
Cognitive decline Physical decline 8% 14% 45%

Control
26% 33% 56%

p
<0.05 <0.05 0.03

Reference

Inouye JAGS 2000

Inouye JAGS 2000 Vidan JAGS 2009

Reduced incident delirium

OR=0.60 RR 35% 6% OR= 0.4

$831 $1.25 million/yr $121,425 0.3 d/pt 3.8 1.2

38%

0.02 0.002 0.03 0.005

Inouye NEJM 1999 Rubin JAGS 2006 Caplan Int Med J 2007 Vidan JAGS 2009

Costs

Rizzo Med care 2001 Rubin JAGS 2006 Caplan Int Med J 2007

LOS Falls /1000 pt days

Rubin JAGS 2006

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

Recognise delirium

Implement preventive strategy (HELP)

Identify and treat cause(s)

Manage symptoms

Drug review

Non-pharmacological

Pharmacological

Infections

Haloperidol

Consider benzodiazepines only for terminal restlessness in last few hours

Delirium
Everybody's problem