Disordered minds and Disordered minds and brains?brains?

Dr Lesley YoungDr Lesley Young

Sunderland Royal HospitalSunderland Royal Hospital

A condition affecting….A condition affecting….

20% all hospital in-patients (40% >80yr olds 20% all hospital in-patients (40% >80yr olds O`Regan et al 2010O`Regan et al 2010))

60-80% ICCU patients (60-80% ICCU patients (50% will develop long-50% will develop long-term cognitive deficitsterm cognitive deficits) ) Ely EDA 2008Ely EDA 2008

And has……..And has…….. 20-30% in-patient mortality20-30% in-patient mortality

(10-14% for acute GI bleed, 4-5% for ACS)(10-14% for acute GI bleed, 4-5% for ACS) 30% institutionalized30% institutionalized Increased complication rateIncreased complication rate Increased length of stayIncreased length of stay 3x increased risk developing dementia3x increased risk developing dementia

Delirium

What I am going to tell youWhat I am going to tell you

DefinitionsDefinitions Why does delirium happen?Why does delirium happen?

– What we can learn from miceWhat we can learn from mice Recognising itRecognising it Risks and precipitantsRisks and precipitants Prevention is better than curePrevention is better than cure Drug treatmentDrug treatment Prognosis and outcomesPrognosis and outcomes

Delirium – DSM IVDelirium – DSM IV

Disturbance of consciousnessDisturbance of consciousness reduced ability to focus, sustain or shift reduced ability to focus, sustain or shift attentionattention

A A change in cognition change in cognition or the development of a or the development of a perceptual disturbance perceptual disturbance that is not due to a pre-that is not due to a pre-existing dementiaexisting dementia

Develops over a Develops over a short period of time short period of time and tends toand tends to fluctuatefluctuate

Evidence that Evidence that disturbance is caused by the disturbance is caused by the direct physiological consequences of a general direct physiological consequences of a general medical condition,medical condition, substance intoxication or substance intoxication or withdrawal.withdrawal.

The get out clause……The get out clause……

Why do old people get Why do old people get delirium with a UTI?delirium with a UTI? Aberrant stress response?Aberrant stress response? Inflammatory theory?Inflammatory theory?

– Systemic infectionSystemic infection– InjuryInjury– surgerysurgery

Cholinergic theory? (↓ Ach →delirium)Cholinergic theory? (↓ Ach →delirium)– Severe illness / trauma →↓ Ach Severe illness / trauma →↓ Ach – Hypoxia/hypoglycaemia →↓ AchHypoxia/hypoglycaemia →↓ Ach– ↑↑SAA →deliriumSAA →delirium

Predisposing factorsPredisposing factors Precipitating Precipitating factorsfactors

High vulnerabilityHigh vulnerability Noxious Noxious insultinsult

Low vulnerabilityLow vulnerability Mild insultMild insult

After Inouye

What we can learn from What we can learn from mice mice (Cunningham)(Cunningham)

Mice with neurodegenerative Mice with neurodegenerative dementia-type disease (ME7)dementia-type disease (ME7)

– Affective (11-13 weeks)Affective (11-13 weeks)– Coginitve (12-16 weeks)Coginitve (12-16 weeks)– Motor (16-19 weeks)Motor (16-19 weeks)– Death (24 weeks)Death (24 weeks)

Effect of inflammatory insult Effect of inflammatory insult on cognitive functionon cognitive function

controls

normal+LCP

prion+LCP

Long term follow up:Long term follow up:accelerated decline in LCP accelerated decline in LCP groupgroup

controls

prion+saline

prion+LCP

ME7 mouse studies have shown ME7 mouse studies have shown a cognitive deficit that:a cognitive deficit that:

Is induced by systemic infectionIs induced by systemic infection Is acute onset and transientIs acute onset and transient Occurs in “demented” but not normal miceOccurs in “demented” but not normal mice Affects working memory > reference Affects working memory > reference

memorymemory Is dependent on prior microglial cell Is dependent on prior microglial cell

activationactivation(After Cunningham EDA 2008-10)(After Cunningham EDA 2008-10)

AgingDementiaPrion disease

Primed microglial cells Infection

InjurySurgery

Other insult

Neuronal death

DELIRIUM

Disease progression

Location of activated microglial

cells determines dysfunction

Activation of microglial cells

In clinical practice.....In clinical practice.....

Identify those at riskIdentify those at risk Prevent incident deliriumPrevent incident delirium Recognise prevalent deliriumRecognise prevalent delirium Identify and treat precipitantsIdentify and treat precipitants Manage behaviour well for better Manage behaviour well for better

outcomesoutcomes

But…..But…..

Delirium is under-recognised:Delirium is under-recognised:– In published studies only 20-50% of In published studies only 20-50% of

cases recorded as delirium in records cases recorded as delirium in records (Collins Age and ageing 2010 28% prevalent delirium detected)(Collins Age and ageing 2010 28% prevalent delirium detected)

Failure to recognize associated with Failure to recognize associated with poor management poor management (Young (Young Age&Ageing 2003Age&Ageing 2003))

Use of cognitive screening tests can Use of cognitive screening tests can improve recognition improve recognition ((Jitapunkul 1991, Anthony Jitapunkul 1991, Anthony Psychol Med 1982, O`Keeffe JAGS 2005, Psychol Med 1982, O`Keeffe JAGS 2005, Young Young Age &Ageing 2003)Age &Ageing 2003)

72.6% cases identified when cognitive screening attempted v 42.9% when not p<0.0001 (Young 2003)

Barriers to recognition Barriers to recognition (Davies et al to (Davies et al to

EDA 2007)EDA 2007)

*p<0.001*p<0.001 Geriatrics Geriatrics experience experience

(n=399)(n=399)

No geriatrics No geriatrics experience experience

(n=351)(n=351)

Confident of diagnostic Confident of diagnostic criteria*criteria*

28%28% 14%14%

Acute onsetAcute onset 89%89% 88%88%

InattentionInattention 32%32% 31%31%

Visual hallucinationsVisual hallucinations 35%35% 38%38%

AgitationAgitation 52%52% 49%49%

Aware of poor prognosisAware of poor prognosis 57%57% 52%52%

Aware under-recognisedAware under-recognised 80%80% 80%80%

Adequate training *Adequate training * 24%24% 9%9%

Aids to recognitionAids to recognition

Cognitive screening Cognitive screening tests:tests:– AMTSAMTS– MMSEMMSE– 6-CIT6-CIT– Sweet 16Sweet 16

Measures of attentionMeasures of attention– Serial 7`sSerial 7`s– Months backwardsMonths backwards– Digit span Digit span

(forwards/backwards)(forwards/backwards)– Trail makingTrail making– Letter cancellation testsLetter cancellation tests

Delirium screening toolsDelirium screening tools– CAMCAM– CAM-ICUCAM-ICU– Delirium Observation Delirium Observation

ScaleScale– NeechamNeecham– DSIDSI

Delirium +/- dementia?Delirium +/- dementia?– Cognitive historyCognitive history– IQCODEIQCODE– AD8AD8– Visual perceptual deficitsVisual perceptual deficits

Risk factorsRisk factors

Age > 75Age > 75 Dementia (2/3 cases)Dementia (2/3 cases) Severe illnessSevere illness Physical frailtyPhysical frailty DehydrationDehydration InfectionInfection Visual impairmentVisual impairment Drugs (opiates, anticholinergics)Drugs (opiates, anticholinergics) SurgerySurgery Alcohol excessAlcohol excess Renal impairmentRenal impairment

PrecipitantsPrecipitants

InfectionInfection DrugsDrugs

– opiods OR 2.5, benzodiazepines OR 3, dihydropyridines OR2.4, opiods OR 2.5, benzodiazepines OR 3, dihydropyridines OR2.4, antihistimines OR 1.8,antihistimines OR 1.8, Clegg and Young Age and Aging 2010Clegg and Young Age and Aging 2010

– Anticholinergic drugs Anticholinergic drugs (Tune REF, Pitkala 2007)(Tune REF, Pitkala 2007)

Dehydration or electrolyte disturbanceDehydration or electrolyte disturbance ImmobilityImmobility MalnutritionMalnutrition Intercurrent illness e.g.Intercurrent illness e.g.

Metabolic/endocrine disturbancesMetabolic/endocrine disturbances Organ failure (liver, renal, cardiac etc)Organ failure (liver, renal, cardiac etc) Neurological problems (e.g. CVA, epilepsy)Neurological problems (e.g. CVA, epilepsy)

Precipitants of delirium – Precipitants of delirium – prospective study General Medical in-patients prospective study General Medical in-patients >70yrs n=87 >70yrs n=87 J Laurila EDA 2009J Laurila EDA 2009

Infections Infections (84%)(84%) DrugsDrugs (46%)(46%) Metabolic disturbanceMetabolic disturbance (47%)(47%) Circulatory conditionsCirculatory conditions (26%)(26%) NeurologicalNeurological (24%)(24%) Other post-opOther post-op (18%)(18%)

Delirium is multi-factorialDelirium is multi-factorial

PreventionPrevention

Up to 40% cases may be preventableUp to 40% cases may be preventable– Early attention to or avoidance of Early attention to or avoidance of

precipitants in those at riskprecipitants in those at risk– Adopting “HELP” approach in those at Adopting “HELP” approach in those at

risk risk (Inouye (Inouye NEJMNEJM 1999; 1999; 340340:669-676):669-676)

Hospital Elder Life Hospital Elder Life Program Program (Inouye NEJM 1999)(Inouye NEJM 1999)

Complications of hospitalisation:Complications of hospitalisation:– Delirium Delirium 25-60%25-60%– Functional declineFunctional decline 34-50%34-50%– Adverse drug eventsAdverse drug events 54%54%

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

Targeted, multi-component intervention programTargeted, multi-component intervention program

Help interventionsHelp interventionsCognitive impairmentCognitive impairment Reality orientationReality orientation

Therapeutic activitiesTherapeutic activities

Vision/hearing Vision/hearing impairmentimpairment

Vision/hearing aidsVision/hearing aids

Adaptive equipmentAdaptive equipment

ImmobilisationImmobilisation Early mobilisationEarly mobilisation

Minimising immobilising Minimising immobilising equipmentequipment

Psychoactive medication Psychoactive medication useuse

Non-pharmacological Non-pharmacological approaches to sleep/anxietyapproaches to sleep/anxiety

Restricted use of sleeping Restricted use of sleeping tabletstablets

DehydrationDehydration Early recognitionEarly recognition

Volume repletionVolume repletion

Sleep deprivationSleep deprivation Noise reduction strategiesNoise reduction strategies

Sleep enhancement programSleep enhancement program

How HELP is delivered - How HELP is delivered - “High touch/low tech”“High touch/low tech” Inclusion criteria:Inclusion criteria:

– Aged 70+Aged 70+– At least one of:At least one of:

MMSE<24MMSE<24 Mobility or ADL Mobility or ADL

impairmentimpairment DehydrationDehydration Vision impairmentVision impairment Hearing impairmentHearing impairment

Screen (by Elder life Screen (by Elder life specialist/nurse)specialist/nurse)– MMSEMMSE– ADLADL– Test vision and hearingTest vision and hearing– Usual activitiesUsual activities

Program delivered by Program delivered by volunteersvolunteers– (16 hours training, 1x4hr (16 hours training, 1x4hr

shift/week for 6/12+)shift/week for 6/12+)

InterventionIntervention ContrControlol

pp ReferenceReference

Cognitive Cognitive declinedecline

8%8% 26%26% <0.0<0.055

Inouye JAGS 2000Inouye JAGS 2000

Physical Physical declinedecline

14%14%

45%45%33%33%

56%56%<0.0<0.055

0.030.03

Inouye JAGS 2000Inouye JAGS 2000

Vidan JAGS 2009Vidan JAGS 2009

Reduced Reduced incident incident deliriumdelirium

OR=0.60OR=0.60

RRRR↓↓ 35% 35%

6%6%

OR= 0.4OR= 0.438%38%

0.020.02

0.000.0022

0.030.03

0.000.0055

Inouye NEJM 1999Inouye NEJM 1999

Rubin JAGS 2006Rubin JAGS 2006

Caplan Int Med J Caplan Int Med J 20072007

Vidan JAGS 2009Vidan JAGS 2009

CostsCosts ↓↓$831$831

↓↓$1.25 million/yr$1.25 million/yr

↓↓$121,425$121,425

Rizzo Med care Rizzo Med care 20012001

Rubin JAGS 2006Rubin JAGS 2006

Caplan Int Med J Caplan Int Med J 20072007

LOSLOS ↓↓0.3 d/pt0.3 d/pt Rubin JAGS 2006Rubin JAGS 2006

Falls Falls /1000 /1000 pt pt daysdays

3.83.8

1.21.211.411.4

4.74.7Inouye NEJM 2009Inouye NEJM 2009

However….However….

Prevention is better than curePrevention is better than cure– HELP (targeted multi-component intervention) HELP (targeted multi-component intervention)

can can preventprevent up to 40% incident delirium up to 40% incident delirium– Little evidence for improved outcomes in Little evidence for improved outcomes in

prevalent delirium prevalent delirium (Laurila, Helsinki study J Geront 2006) (Laurila, Helsinki study J Geront 2006) at at 6/12:6/12:

MMSE Sl better in intervention groupMMSE Sl better in intervention group QoL Sl better in intervention groupQoL Sl better in intervention group Costs of care – no differentCosts of care – no different

How should we treat How should we treat prevalent delirium?prevalent delirium? Identify and treat underlying causeIdentify and treat underlying cause

Drugs?Drugs?– Neuroleptics??Neuroleptics??– Benzodiazepines??Benzodiazepines??– Cholinesterase inhibitors??Cholinesterase inhibitors??

Investigating the causeInvestigating the cause

Infections:Infections:– CulturesCultures

MSU, sputum, MSU, sputum, swabs etcswabs etc

– FBCFBC– CRPCRP– CXRCXR– LP LP (only if clinical picture (only if clinical picture

points to CNS cause)points to CNS cause)

Drug reviewDrug review– Stop what you canStop what you can

Metabolic upsetsMetabolic upsets– U&E, LFT, Ca, TFT, U&E, LFT, Ca, TFT,

GlucoseGlucose

CirculatoryCirculatory– ECGECG

NeurologicalNeurological– CT CT (often abnormal, rarely (often abnormal, rarely

diagnostic – consider if likely diagnostic – consider if likely acute CNS cause)acute CNS cause)

– EEG EEG (? Non-convulsive (? Non-convulsive status, HSE, dementia v status, HSE, dementia v delirium)delirium)

DrugsDrugs

Cochrane database 2009Cochrane database 2009 Benzos – not recommendedBenzos – not recommended Cholinesterase inhibitors – no evidenceCholinesterase inhibitors – no evidence Antipsychotics – effective over placeboAntipsychotics – effective over placebo Haloperidol effective over lorazepamHaloperidol effective over lorazepam

Treatment trials are rare and difficultTreatment trials are rare and difficult RCTs antipsychoticsRCTs antipsychotics

RCTs antipsychoticsRCTs antipsychotics

Risperidone = olanzepineRisperidone = olanzepineRisperidone = haloperidolRisperidone = haloperidolQuetiapine > placeboQuetiapine > placeboDexmetomedine > haloperidol (ICU)Dexmetomedine > haloperidol (ICU)Olanzepine = haloperidol (ICCU)Olanzepine = haloperidol (ICCU)Olanzepine > haloperidol (chinese dementia)Olanzepine > haloperidol (chinese dementia)Amisulpiride = quetipineAmisulpiride = quetipineHaloperidol/chlorpromazine > lorazepamHaloperidol/chlorpromazine > lorazepam

RCP/BGS guidelines - haloperidolRCP/BGS guidelines - haloperidol EDA 2009 consensus - haloperidolEDA 2009 consensus - haloperidol NICE 2010– haloperidol or olanzepineNICE 2010– haloperidol or olanzepine

Low dose, minimum duration, to alleviate distressLow dose, minimum duration, to alleviate distress

Cholinesterase inhibitorsCholinesterase inhibitors

Theoretical basis why Cholinestersae Theoretical basis why Cholinestersae inhibitors might be helpful......BUTinhibitors might be helpful......BUT

Several small studies – results inconclusiveSeveral small studies – results inconclusive Rivastigmine does not decrease duration of Rivastigmine does not decrease duration of

delirium and may increase mortality delirium and may increase mortality (Eijk 2010)(Eijk 2010)

– Multicentre, double-blind placebo-controlled RCT Multicentre, double-blind placebo-controlled RCT in ICU patients with deliriumin ICU patients with delirium

– Trial stopped after 104 patients included because Trial stopped after 104 patients included because increased mortality and trend to increased increased mortality and trend to increased duration of delirium in treatment groupduration of delirium in treatment group

PrognosisPrognosis

Traditional view:Traditional view:– Short, transient, full recoveryShort, transient, full recovery

Delirium research shows:Delirium research shows:– Poor outcomes even with full recoveryPoor outcomes even with full recovery– Independent predictor of poor outcomeIndependent predictor of poor outcome

Recovery from delirium Recovery from delirium (cole (cole

EDA 2008)EDA 2008)

55% improved at 1 month55% improved at 1 month 70% improved at 6 months (i.e. 30% not)70% improved at 6 months (i.e. 30% not)

A substantial minority of patients don`t A substantial minority of patients don`t recover (~10%)recover (~10%)

Full recovery associated with good Full recovery associated with good outcomes (= no delirium)outcomes (= no delirium)

Incomplete recovery may impair self Incomplete recovery may impair self management management worse outcomesworse outcomes

20-30% in-patient mortality20-30% in-patient mortality 30% institutionalized30% institutionalized Increased complication rateIncreased complication rate Increased length of stayIncreased length of stay 3x increased risk developing dementia3x increased risk developing dementia

Copyright restrictions may apply.

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

Adjusted Total 1-Year Health Care Costsa

Relation between delirium Relation between delirium and dementiaand dementia

1.Delirium Dementia (causal)

Delirium (marker)

2. Subclinical dementia Dementia

Delirium

3. Insult Dementia

Probably 1+2

ConclusionConclusion

Delirium is commonDelirium is common Under-recognised and low priorityUnder-recognised and low priority Associated with poor outcomesAssociated with poor outcomes Prevention is possible and cost Prevention is possible and cost

effective in those at riskeffective in those at risk Prevention is better than curePrevention is better than cure

Infection controlInfection control Confusion controlConfusion control

Thank youThank you