Transcript Delerium

Delerium, Dementia and
Insomnia
14th Feb 2006
Delerium
Delirium - “to go out of the furrow”
Acute Confusional State







30% of elderly medical inpatients
High Mortality
High Morbidity
Longer hospital stays
Predicts institutionalisation
Often missed
Poorly managed
Diagnosis of Delirium

Disturbance of consciousness with reduced ability to
focus, sustain or shift attention

Change in cognition or perceptual disturbance

Short period of time (hours to days) and fluctuates

Caused by the direct physiological consequences of a
general medical condition, substance intoxication or
substance withdrawal
Differential Diagnosis

Dementia
- AMT / MMSE cannot distinguish
- often delerium superimposed on dementia

Psychotic illness
Delirium vs Dementia






Collateral history
Acute onset, short duration
Reduced consciousness
Diurnal fluctuation
Hallucinations common
Physical precipitant
Risk factors









Age
Dementia
Severe illness
Physical frailty
Infection/dehydration
Sensory impairment
Polypharmacy
Excess alcohol
Psychosocial stresses
Common Causes










Infection
Drugs
Neurological
Cardiac
Respiratory
Pain
Electrolytes
Endocrine/metabolic
Nutritional
Often multiple aetiologies
Drug classes commonly
implicated in Delirium








Opiates
Anticholinergics
Sedative/hypnotics including withdrawal
Dopamine agonists
Antidepressants
Alcohol withdrawal
Corticosteroids
Lithium
Investigations - for all










FBC
Calcium
Urea and electrolytes
LFTs
Glucose
TFTs
CXR
ECG
Blood cultures
Urinalysis
Investigations - when indicated






ABG
B12 & Folate
Specific cultures
Lumbar puncture
CT head
EEG
CT Brain Scanning

Not helpful if performed routinely

Focal neurological signs

Confusion following head injury

Confusion following a fall

Raised intracranial pressure
EEG

Limited use

Delirium versus dementia

Non-convulsive status epilepticus

Focal intracranial lesions
Management







Identify and treat the underlying cause
Evaluate response (monitor AMT)
Optimum environment
Multidisciplinary team
Avoid physical restraints
Avoid major tranquilizers where possible
Control dangerous and disruptive behavior
Psychotropic medication

To prevent harm or allow evaluation and treatment

Low-dose haloperidol (0.5 to 1.0 mg orally or
intramuscularly) to control agitation or psychotic symptoms

MOA: D2 dopamine receptor antagonist

Low frequency of sedation and hypotension

Onset of action is 30 to 60 minutes after parenteral
administration or longer with the oral route

s/e extrapyramidal; neuroleptic malignant syndrome

Atypical antipsychotics - ↑ risk cerebrovascular disease
Benzodiazepines

Benzodiazepines (eg, lorazepam 0.5 to 1.0 mg po/IM) have a
more rapid onset of action (five minutes after parenteral
administration)

Commonly worsen confusion and sedation

Drugs of choice in cases of sedative drug and alcohol
withdrawal

May be useful adjuncts to neuroleptics to promote light
sedation and reduce extrapyramidal side effects
Alois Alzheimer
1864-1915
Dementia



A general decrease in the level of cognition,
especially memory
Behavioral disturbance
Interference with daily function and
independence
Dementia syndromes







Alzheimer's disease (AD) 60-80%
Vascular dementia (VaD) 10-20%
Dementia with Lewy bodies (DLB) 10%
Parkinson's disease with dementia (PDD) 5%
Fronto-temporal dementia (FTD)
Reversible dementias
Others eg alcoholic
Cholinergic Deficit
Alzheimer's disease
(AD) sufferers have
reduced cerebral
production of choline
acetyl transferase &
impaired cortical
cholinergic function
Cholinesterase inhibitors

MOA: increase cholinergic transmission by inhibiting
cholinesterase at the synaptic cleft

Tacrine (abn LFTs), donepezil od, rivastigmine bd, and
galantamine

s/e: insomnia; nausea; diarrhoea; syncope; BP changes;
arrhythmias

Int: anticholinergics; antipsychotics
Evidence of Efficacy

13 RCTs

treatment for 6 months - 1 year

mild, moderate or severe dementia due to Alzheimer's disease

improvements in cognitive function

-2.7 points (95%CI -3.0 to -2.3), in the midrange of the 70
point ADAS-Cog Scale

↑ clinical global measures

Delay disease progression

Conflicting data on cost effectiveness
NMDA Receptor antagonists
Excessive N-methyl-Daspartate (NMDA)
receptor stimulation
can be induced by
ischemia and lead to
excitotoxicity
Memantine

MOA: low affinity glutamate NMDA receptor antagonist

Ind: Moderate to severe VaD, AD

small beneficial effect at six months

1.85 ADAS-Cog points, 95% CI 0.88 to 2.83

Agents that block pathologic stimulation of NMDA receptors
may protect against further damage in patients with vascular
dementia

s/e Dizziness, agitation, delusions
Antioxidants




Vitamin E
Selegiline (MAO-B
inhibitor)
Delayed nursing
home placement
No evidence of
benefit on cognition
Selegiline and Vitamin E: Delay in
Clinical Progression of
Alzheimer's Disease
Ginkgo Biloba






Chinese herbal medicine
Contains flavoglycosides
potent free radical scavengers
inhibit platelet-activating factor (PAF)
May improve regional circulation
May improve cholinergic
neurotransmission
Ginkgo Biloba






Ginkgo Biloba (Meta-analysis of RCTs)
Four studies with 212 subjects in each placebo and drug groups
using EGb 761 120–240 mg/day
Results: small but significant effect of 3–6 month treatment 120–240
mg of Gingko biloba extract on objective measures of cognitive
function
Side effects: four reports of hemorrhage
Caution: in patients taking anticoagulants, antiplatelets or with
bleeding diathesis
lack of regulation, including variability in the dosing and contents of
herbal extracts
Agents with no clear benefit or
evidence of harm



Oestrogen/testosterone replacement
NSAIDS
immunization with amyloid beta
peptide (6% meningoencephalitis)
Behavioral symptoms

Agitation

Aggression

Delusions

Hallucinations

wandering
Behavioral symptoms

depression and sleep disturbances

depressive pseudodementia

concomitant medical illness

medication toxicity

behavioral methods
Treatment of behavioral
symptoms

Non-pharmacological
- look for medical cause
eg: constipation, urinary retention, infection, drug toxicity,
pain, delirium
- look for an environmental cause
eg: fear of unrecognized caregivers, trigger of the behavior,
sensory deprivation
Treatment of behavioral
symptoms


Antipsychotic agents
Atypical 1.6- to 1.7 fold increase in mortality compared with
placebo

Typical agents have problems with extrapyramidal s/e

Antidepressants

SSRIs preferable

Benzodiazepines worsening gait, potential paradoxical
agitation, and possible physical dependence
Insomnia
Insomnia

inadequate quantity or quality of sleep

difficulty initiating or maintaining sleep

Non-restorative sleep/impaired daytime functioning

Persistent insomnia is usually a consequence of
medical, neurologic or psychiatric disease
Assessment



Alcohol and drug history
- central nervous system stimulants
- withdrawal of CNS depressant drugs
Treatment of co-morbid insomnia is unlikely to be
successful unless the primary cause of the
disturbance is diagnosed and properly remedied
Nonpharmacologic measures in conjunction with
the judicious use of hypnotics
Who should be prescribed hypnotics?



Judicious use of hypnotics may be helpful when treating
transient or short-term idiopathic or psychophysiologic
insomnia
Short courses to alleviate acute insomnia after causal factors
have been established
Some patients with insomnia benefit from long term hypnotics
without evidence of tolerance or abuse
Who should not?

Contraindicated in pregnancy

Avoid or use judiciously in patients with alcoholism or renal,
hepatic, or pulmonary disease

Avoid in patients with sleep apnea syndrome

Avoid concomitant alcohol ingestion

Avoid where high risk of abuse/dependence

Avoid where altered performance may be detrimental
eg driving, on-call, carers
Historical agents






Laudanum
Bromide 19th C
Chloral hydrate
Clomethiazole
Barbiturates
Chlordiazepoxide 1960s
Hypnotic agents

Benzodiazepines

Nonbenzodiazepine drugs

Sedating antidepressants eg, amitriptyline, trazodone

Antihistamines diphenhydramine

Valerian – no clear evidence of effectiveness

Melatonin - large doses sold over-the-counter may be associated
with side effects, such as hypothermia, gynecomastia, seizures

Melatonin receptor agonists - unpublished trials
Benzodiazepines



Low capacity to produce fatal CNS depression
MOA: enhance effects of the inhibitory neurotransmitter, GABA
on the GABA A receptor
Sedative, hypnotic, muscle relaxant, anxiolytic, anticonvulsant,
anterograde amnesia

Increase total sleep time but shortened time in REM sleep

Most have active metabolites with long t1/2
Adverse effects of BZDs

Can get rebound insomnia on withdrawal esp with short-acting agents

Residual somnolence esp with long-acting agents

Tolerance

Dependence and abuse

↑ falls risk in elderly

Delirium in elderly

Withdrawal – confusion, convulsions, DTs

Up to 3 weeks after long-acting agent

Paradoxical effects

Anterograde amnesia
Nonbenzodiazepine hypnotics



nonbenzodiazepine drugs
eg zolpidem, zaleplon, zopiclone
also activate the benzodiazepine
receptor, although they do not have a
benzodiazepine structure
Nonbenzodiazepine hypnotics




at hypnotic doses less muscle relaxation or
memory-disrupting effects
↓ tolerance and dependence
Less effects on REM sleep
Short half-life of ±2 hours and elimination
by liver metabolism - minimal sedation the
next day after administration
Azapirones




MOA: 5HT1A agonists
Eg Buspirone
Mild to moderate anxiety
No tolerance or withdrawal