Delerium, Dementia and Insomnia

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Delerium, Dementia and Insomnia

• 14th Feb 2006

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Delerium
Delirium - to go out of the furrow
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Acute Confusional State

• 30 of elderly medical inpatients
• High Mortality
• High Morbidity
• Longer hospital stays
• Predicts institutionalisation
• Often missed
• Poorly managed

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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

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Differential Diagnosis

• Dementia
• - AMT / MMSE cannot distinguish
• - often delerium superimposed on dementia
• Psychotic illness

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Delirium vs Dementia

• Collateral history
• Acute onset, short duration
• Reduced consciousness
• Diurnal fluctuation
• Hallucinations common
• Physical precipitant

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Risk factors

• Age
• Dementia
• Severe illness
• Physical frailty
• Infection/dehydration
• Sensory impairment
• Polypharmacy
• Excess alcohol
• Psychosocial stresses

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Common Causes

• Infection
• Drugs
• Neurological
• Cardiac
• Respiratory
• Pain
• Electrolytes
• Endocrine/metabolic
• Nutritional
• Often multiple aetiologies

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Drug classes commonly implicated in Delirium

• Opiates
• Anticholinergics
• Sedative/hypnotics including withdrawal
• Dopamine agonists
• Antidepressants
• Alcohol withdrawal
• Corticosteroids
• Lithium

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Investigations - for all

• FBC
• Calcium
• Urea and electrolytes
• LFTs
• Glucose
• TFTs
• CXR
• ECG
• Blood cultures
• Urinalysis

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Investigations - when indicated

• ABG
• B12 Folate
• Specific cultures
• Lumbar puncture
• CT head
• EEG

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CT Brain Scanning

• Not helpful if performed routinely
• Focal neurological signs
• Confusion following head injury
• Confusion following a fall
• Raised intracranial pressure

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EEG

• Limited use
• Delirium versus dementia
• Non-convulsive status epilepticus
• Focal intracranial lesions

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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

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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

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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

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• Alois Alzheimer 1864-1915

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Dementia

• A general decrease in the level of cognition,
  especially memory
• Behavioral disturbance
• Interference with daily function and
  independence

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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

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Cholinergic Deficit

• Alzheimer's disease (AD) sufferers have
  reduced cerebral production of choline acetyl
  transferase impaired cortical cholinergic
  function

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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

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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 (95CI -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

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NMDA Receptor antagonists

• Excessive N-methyl-D-aspartate (NMDA) receptor
  stimulation can be induced by ischemia and lead
  to excitotoxicity

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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

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Antioxidants
Selegiline and Vitamin E Delay in Clinical
Progression of Alzheimer's Disease

• Vitamin E
• Selegiline (MAO-B inhibitor)
• Delayed nursing home placement
• No evidence of benefit on cognition

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Ginkgo Biloba

• Chinese herbal medicine
• Contains flavoglycosides
• potent free radical scavengers
• inhibit platelet-activating factor (PAF)
• May improve regional circulation
• May improve cholinergic neurotransmission

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Ginkgo Biloba

• Ginkgo Biloba (Meta-analysis of RCTs)
• Four studies with 212 subjects in each placebo
  and drug groups using EGb 761 120240 mg/day
• Results small but significant effect of 36
  month treatment 120240 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

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Agents with no clear benefit or evidence of harm

• Oestrogen/testosterone replacement
• NSAIDS
• immunization with amyloid beta peptide (6
  meningoencephalitis)

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Behavioral symptoms

• Agitation
• Aggression
• Delusions
• Hallucinations
• wandering

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Behavioral symptoms

• depression and sleep disturbances
• depressive pseudodementia
• concomitant medical illness
• medication toxicity
• behavioral methods

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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

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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

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Insomnia
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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

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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

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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

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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
  

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Historical agents

• Laudanum
• Bromide 19th C
• Chloral hydrate
• Clomethiazole
• Barbiturates
• Chlordiazepoxide 1960s

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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

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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

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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

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Nonbenzodiazepine hypnotics

• nonbenzodiazepine drugs
• eg zolpidem, zaleplon, zopiclone
• also activate the benzodiazepine receptor,
  although they do not have a benzodiazepine
  structure

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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

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Azapirones

• MOA 5HT1A agonists
• Eg Buspirone
• Mild to moderate anxiety
• No tolerance or withdrawal