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Precipitants of delirium

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Precipitants of delirium Powered By Docstoc
					Disordered minds and
       brains?
    Dr Lesley Young
Sunderland Royal Hospital
A condition affecting….
   20% all hospital in-patients (40% >80yr
    olds O`Regan et al 2010)
   60-80% ICCU patients (50% will develop long-
    term cognitive deficits) Ely EDA 2008
And has……..
   20-30% in-patient mortality
    (10-14% for acute GI bleed, 4-5% for ACS)
   30% institutionalized
   Increased complication rate
   Increased length of stay
   3x increased risk developing dementia
Delirium
What I am going to tell you

   Definitions
   Why does delirium happen?
    – What we can learn from mice
   Recognising it
   Risks and precipitants
   Prevention is better than cure
   Drug treatment
   Prognosis and outcomes
Delirium – 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……
Why do old people get
delirium with a UTI?
   Aberrant stress response?
   Inflammatory theory?
    – Systemic infection
    – Injury
    – surgery
   Cholinergic theory? (↓ Ach →delirium)
    – Severe illness / trauma →↓ Ach
    – Hypoxia/hypoglycaemia →↓ Ach
    – ↑SAA →delirium
Predisposing factors   Precipitating factors
High vulnerability            Noxious insult




Low vulnerability             Mild insult




                                  After Inouye
What we can learn from
mice (Cunningham)
   Mice with neurodegenerative
    dementia-type disease (ME7)
         –   Affective (11-13 weeks)
         –   Coginitve (12-16 weeks)
         –   Motor (16-19 weeks)
         –   Death (24 weeks)
Effect of inflammatory insult
on cognitive function




                         controls
                         normal+LCP
                         prion+LCP
Long term follow up:
accelerated decline in LCP
group


                         controls
                         prion+saline
                         prion+LCP
ME7 mouse studies have shown
a cognitive deficit that:

   Is induced by systemic infection
   Is acute onset and transient
   Occurs in “demented” but not normal
    mice
   Affects working memory > reference
    memory
   Is dependent on prior microglial cell
    activation
                     (After Cunningham EDA 2008-10)
Aging
Dementia        Primed microglial
                     cells              Infection
Prion disease                             Injury
                                         Surgery
                                       Other insult

                   Activation of
                    microglial
                    cells




                    DELIRIUM
  Location of
   activated                        Neuronal death
   microglial
     cells
  determines
  dysfunction          Disease
                     progression
In clinical practice.....

   Identify those at risk
   Prevent incident delirium
   Recognise prevalent delirium
   Identify and treat precipitants
   Manage behaviour well for better
    outcomes
But…..
   Delirium is under-recognised:
     – In published studies only 20-50% of
       cases recorded as delirium in records
       (Collins Age and ageing 2010 28% prevalent delirium detected)
   Failure to recognize associated with
    poor management (Young Age&Ageing 2003)
   Use of cognitive screening tests can
    improve recognition (Jitapunkul 1991, Anthony
    Psychol Med 1982, O`Keeffe JAGS 2005, Young Age &Ageing 2003)
          72.6% cases identified when cognitive screening attempted v
           42.9% when not p<0.0001 (Young 2003)
Barriers to recognition
EDA 2007)
                                                (Davies et al to



*p<0.001                       Geriatrics   No geriatrics
                              experience     experience
                               (n=399)        (n=351)
Confident of diagnostic         28%            14%
criteria*
            Acute onset          89%            88%
            Inattention          32%            31%
      Visual hallucinations      35%            38%
             Agitation           52%            49%
Aware of poor prognosis          57%            52%

Aware under-recognised           80%            80%

Adequate training *             24%             9%
Aids to recognition
   Cognitive screening              Delirium screening
    tests:                            tools
    –   AMTS                          – CAM
    –   MMSE                          – CAM-ICU
    –   6-CIT                         – Delirium Observation
    –   Sweet 16                        Scale
                                      – Neecham
   Measures of attention             – DSI
    – Serial 7`s
    – Months backwards               Delirium +/- dementia?
    – Digit span                      –   Cognitive history
      (forwards/backwards)            –   IQCODE
    – Trail making                    –   AD8
    – Letter cancellation tests       –   Visual perceptual deficits
Risk factors
   Age > 75
   Dementia (2/3 cases)
   Severe illness
   Physical frailty
   Dehydration
   Infection
   Visual impairment
   Drugs (opiates, anticholinergics)
   Surgery
   Alcohol excess
   Renal impairment
Precipitants
   Infection
   Drugs
    – opiods OR 2.5, benzodiazepines OR 3, dihydropyridines OR2.4,
      antihistimines OR 1.8, Clegg and Young Age and Aging 2010
    – Anticholinergic drugs (Tune REF, Pitkala 2007)
   Dehydration or electrolyte disturbance
   Immobility
   Malnutrition
   Intercurrent illness e.g.
           Metabolic/endocrine disturbances
           Organ failure (liver, renal, cardiac etc)
           Neurological problems (e.g. CVA, epilepsy)
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%)


       Delirium is multi-factorial
Prevention

   Up to 40% cases may be preventable
    – Early attention to or avoidance of
      precipitants in those at risk
    – Adopting “HELP” approach in those at
      risk (Inouye NEJM 1999; 340:669-676)
Hospital Elder Life
Program (Inouye NEJM 1999)
   Complications of hospitalisation:
    – Delirium                 25-60%
    – Functional decline       34-50%
    – Adverse drug events      54%

    –   *HAI                   17%
    –   *Falls                 15%
    –   *Pressure sores        10%
    –   *VTE                   3%

   Targeted, multi-component intervention
    program
 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
How HELP is delivered -
“High touch/low tech”
   Inclusion criteria:             Screen (by Elder
    – Aged 70+                       life specialist/nurse)
    – At least one of:               – MMSE
           MMSE<24
           Mobility or ADL
                                     – ADL
            impairment               – Test vision and
           Dehydration                hearing
           Vision impairment
                                     – Usual activities
           Hearing impairment
                                    Program delivered
                                     by volunteers
                                     – (16 hours training, 1x4hr
                                       shift/week for 6/12+)
            Intervention        Control p      Reference

Cognitive   8%                  26%    <0.05 Inouye JAGS 2000
decline
Physical    14%                 33%    <0.05 Inouye JAGS 2000
decline     45%                 56%    0.03 Vidan JAGS 2009
Reduced     OR=0.60                    0.02    Inouye NEJM 1999
incident    RR↓ 35%                    0.002   Rubin JAGS 2006
delirium    6%                  38%    0.03    Caplan Int Med J 2007
            OR= 0.4                    0.005   Vidan JAGS 2009
Costs       ↓$831                              Rizzo Med care 2001
            ↓$1.25 million/yr                  Rubin JAGS 2006
            ↓$121,425                          Caplan Int Med J 2007
LOS         ↓0.3 d/pt                          Rubin JAGS 2006

Falls /1000 3.8                 11.4           Inouye NEJM 2009
pt days
            1.2                 4.7
However….

   Prevention is better than cure
    – HELP (targeted multi-component
      intervention) can prevent up to 40%
      incident delirium
    – Little evidence for improved outcomes in
      prevalent delirium (Laurila, Helsinki study J Geront
      2006) at 6/12:
        MMSE Sl better in intervention group
        QoL Sl better in intervention group

        Costs of care – no different
How should we treat
prevalent delirium?
   Identify and treat underlying cause

   Drugs?
    – Neuroleptics??
    – Benzodiazepines??
    – Cholinesterase inhibitors??
Investigating the cause
   Infections:                           Metabolic upsets
    – Cultures                             – U&E, LFT, Ca, TFT,
            MSU, sputum,                    Glucose
             swabs etc
                                          Circulatory
    –   FBC
    –   CRP                                – ECG
    –   CXR                               Neurological
    –   LP (only if clinical picture       – CT (often abnormal,
        points to CNS cause)                 rarely diagnostic –
                                             consider if likely acute
   Drug review                              CNS cause)
    – Stop what you can                    – EEG (? Non-convulsive
                                             status, HSE, dementia v
                                             delirium)
Drugs

   Cochrane database 2009
        Benzos – not recommended
        Cholinesterase inhibitors – no evidence

        Antipsychotics – effective over placebo

        Haloperidol effective over lorazepam

   Treatment trials are rare and difficult
   RCTs antipsychotics
RCTs antipsychotics
Risperidone = olanzepine
Risperidone = haloperidol
Quetiapine > placebo
Dexmetomedine > haloperidol (ICU)
Olanzepine = haloperidol (ICCU)
Olanzepine > haloperidol (chinese dementia)
Amisulpiride = quetipine
Haloperidol/chlorpromazine > lorazepam


   RCP/BGS guidelines - haloperidol
   EDA 2009 consensus - haloperidol
   NICE 2010– haloperidol or olanzepine

Low dose, minimum duration, to alleviate distress
Cholinesterase inhibitors

   Theoretical basis why Cholinestersae
    inhibitors might be helpful......BUT
   Several small studies – results inconclusive
   Rivastigmine does not decrease duration of
    delirium and may increase mortality (Eijk 2010)
    – Multicentre, double-blind placebo-controlled RCT
      in ICU patients with delirium
    – Trial stopped after 104 patients included
      because increased mortality and trend to
      increased duration of delirium in treatment group
        Prognosis

   Traditional view:
    – Short, transient, full recovery

   Delirium research shows:
    – Poor outcomes even with full recovery
    – Independent predictor of poor outcome
Recovery from delirium (cole
EDA 2008)


 55% improved at 1 month
 70% improved at 6 months (i.e. 30%
  not)
A substantial minority of patients don`t
  recover (~10%)
Full recovery associated with good
  outcomes (= no delirium)
Incomplete recovery may impair self
  management         worse outcomes
   20-30% in-patient mortality
   30% institutionalized
   Increased complication rate
   Increased length of stay
   3x increased risk developing dementia
                                      Adjusted Total 1-Year Health Care Costsa




Leslie, D. L. et al. Arch Intern Med 2008;168:27-32.

  Copyright restrictions may apply.
Relation between delirium
and dementia
1.Delirium      Dementia (causal)

                        Delirium (marker)
2. Subclinical dementia            Dementia

                Delirium
3. Insult       Dementia
                                Probably 1+2
Conclusion

   Delirium is common
   Under-recognised and low priority
   Associated with poor outcomes
   Prevention is possible and cost
    effective in those at risk
   Prevention is better than cure
Infection control   Confusion control
Thank you

				
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