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Delirium ageing&health at southampton Thursday 21 st March 2013 Acute Medicine Update - 7 Southampton Dr Joe Butchart SpR in Geriatric Medicine / Clinical.

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Presentation on theme: "Delirium ageing&health at southampton Thursday 21 st March 2013 Acute Medicine Update - 7 Southampton Dr Joe Butchart SpR in Geriatric Medicine / Clinical."— Presentation transcript:

1 Delirium ageing&health at southampton Thursday 21 st March 2013 Acute Medicine Update - 7 Southampton Dr Joe Butchart SpR in Geriatric Medicine / Clinical Research Fellow Memory Assessment and Research Centre University of Southampton Faculty of Medicine

2 Overview What is delirium? How is it diagnosed? What is the evidence for current treatment? What do we know about the biology of delirium? What does the future hold?

3 Delirium: DSM-IV 1.Disturbance of consciousness (i.e. reduced clarity of awareness of the environment) with reduced ability to focus, sustain or shift attention. 2.A change in cognition (such as memory deficit, disorientation, language disturbance) 3.The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. 4.Evidence of a precipitating general medical condition, substance intoxication or substance withdrawal.

4 Delirium: ICD-10 Impairment of consciousness and attention Global disturbance of cognition, perceptual, abstract thought, memory, orientation in time Psychomotor disturbance (hypo or hyperactivity, or both) Altered sleep-wake cycle, symptoms worse at night Emotional disturbance (depression, anxiety, fear, irritability, euphoria, perplexity)

5 High incidence of delirium in hospitalized patients In-patients: 10 - 31% Hip fracture: 47 – 61% General post-op: 15 – 53% Intensive Care: 70 – 87% Palliative care: 8 – 85% Under-detected: 33 – 66% Inouye (2006), Siddiqi (2006), Pisani (2003), Collins (2011)

6 Predisposing Dementia (22 – 89%) Age Male gender OR 1.9 (95% CI 1.4 to 2.6) Depression Alcohol abuse Frailty or co-morbidities Poor mobility Sensory impairment Low Albumin Precipitating Medical illness OR 3.8 (95% CI 2.2 to 6.4) Surgery Drugs Sleep deprivation Ward moves Dehydration Immobility Pain Malnutrition Renal failure Urinary catheterisation Fick (2002), Elie (1998), Inouye (2006), Marcantonio (1994), Schorl (1992), Pompei (1994)

7 Patients with delirium have poor outcomes Mortality: HR 1.95 (95% CI 1.51 to 2.52) independent of prior dementia diagnosis Long-term care placement: OR 2.41 (95% CI 1.77 to 3.29) Developing dementia: OR 12.52 (95% CI 1.86 to 84.21) Accelerated cognitive decline in AD 1.96 x Rate of Decline, p=0.001 Witlox (2010), Siddiqi (2006), Babar (2012), Rudolph (2010), Fong (2009)

8 Diagnosis of delirium Is it present? What is the precipitating cause?

9 Delirium Acute onset and fluctuating course CognitionAttention Consciousness or Alertness Disengaged Lethargic Stupor Aroused Hypervigilant Disorientation in time (especially judgment of the passage of time) is earliest to appear and last to resolve Disordered thinking Incoherence Illogical flow of ideas Misperceptions Hallucinations Paranoia Memory loss ability to focus, sustain or shift attention “accessibility” during conversation or AMTS failure to shift attention causes perseveration Most common feature in older patients is a relatively quiet, withdrawn state, frequently mistaken for depression

10 Confusion Assessment Method (CAM) 1.Presence of acute onset and fluctuating course AND 2.Inattention (e.g. 20-1 test with reduced ability to maintain attention or shift attention) AND EITHER 3.Disorganised thinking (disorganised or incoherent speech) OR 4.Altered level of consciousness (usually lethargy or stupor, sometimes hyper-alert) Inouye (1990), NICE (2010), BGS (2005) Sensitivity: 94 – 100% Specificity: 90 – 95% Review of 11 bedside delirium tests CAM was best, MMSE worst Wong (JAMA 2010)

11 CAM – the non-validated way! A Acute onset and fluctuating course B Bad attention C Consciousness altered (drowsy, hyper-alert) D Disorganised thinking

12 Differential diagnosis Dementia Depression Mania Schizophrenia Dysphasia Non convulsive epilepsy (present in 37% of patients referred for EEG because of altered consciousness) Privitera (1994)

13 Precipitants of delirium Infections UTI, chest Urinary retention Pain Drugs BZD, neuroleptics, opiates Drug & Alcohol withdrawal Endocrine & Metabolic Cachexia, ↓thiamine, ↓T4 Respiratory Hypoxia, PE Electrolyte imbalance Dehydration, ↓Na, AKI Cardiac MI, Heart failure Neurological Stroke, SDH, encephalitis Faecal impaction But remember: In delirium the last place you look is the brain!

14 Investigations Pulse oximetry ECG FBC and CRP U&E, calcium, glucose LFTs Thyroid function B12 and Folate Urinalysis Chest X ‑ ray Blood cultures Specific cultures eg urine, sputum Arterial blood gases CT head (with specific indication) Lumbar puncture EEG (rarely)

15 Evidence-based management Prevention Non-pharmacological Pharmacological Treatment of established delirium Non-pharmacological Pharmacological

16 HELP: Hospital Elder Life Program (6 interventions): Cognitive re-orientation Sleep hygiene Mobilisation Vision Hearing Hydration Implementation: geriatricians and trained volunteers 852 patients Incidence of delirium 9.9% vs 15% OR 0.60 (95% CI 0.39 to 0.92)

17 Journal of the American Geriatrics Society 2001; 49: 516-522 Oxygenation Hydration / electrolytes Pain management Medication review Bowel / Bladder Nutrition Mobilisation Post-op complications Environment Management delirium Delirium in 50% of hip fracture patients Geriatrician consultation (daily visits, 10 point structured protocol) Recommendations made in >70% of patients: 1.Transfuse to haematocrit >30% 2.Urinary catheter out by Day 2 post-op 3.Changes to psychoactive drugs 4.Regular paracetamol for pain 126 patients Delirium: 32% vs 50% (p=0.04) Severe delirium: 12% vs 29% (p=0.02)

18 Intervention: Pre-operative Comprehensive Geriatric Assessment Medical optimisation (eg BP control) Education on exercise, nutrition, pain management OT/Physio anticipate discharge needs Post-op geriatrician / nurse specialist review Attention to medical complications, early mobilisation, pain control, bowel/bladder function, nutrition, early discharge planning Home follow-up POPS vs Routine pre and post-op care Delirium: 6% vs 19% (p=0.036) Pneumonia: 4% vs 20% (p=0.008) Pressure sores: 4% vs 19% (p=0.028)

19 Prevention: pharmacological trials Haloperidol 0.5mg TDS for 3/7 after hip surgery Olanzapine 5mg BD for 1/7 after hip/knee surgery Low dose IV haloperidol after major surgery Kalisvaart (2005), Larsen (2010), Wang (2012) Reduced incidence Reduced severity Antipsychotics convert hyperactive delirium to hypoactive delirium Hypoactive delirium is harder to diagnose Severity scales tend to give hyperactive symptoms high weightings Reduced severity and reduced incidence may just be conversion to hypoactive delirium Outcomes for hypoactive delirium often WORSE No studies show improved long term outcomes

20 Prevention: pharmacological Cholinesterase inhibitors (donepezil etc): Elective ortho: No benefit ITU: ↑Mortality Memantine: No benefit Hshieh (2008), Liptzin (2005), van Eijk (2010), Marcantonio (2011)

21 Prevention: pharmacological trials Anaesthetic agents GA vs regional anaesthesia: no sig difference Light sedation vs Heavy sedation ↓ delirium 19% vs 40% (p<0.01) Melatonin in general medical patients ↓ delirium 12% vs 31% (p<0.02) (on-going MAPLE trial) Seiber (2009), de Jonghe (2011)

22 Treatment Very scant evidence base Non-pharmacological Pharmacological

23 Treatment: non-pharmacological GroupInterventionResult Cole et al. CMAJ 2002 Systematic detection, specialised care Trend towards faster cognitive recovery Pitkala et al. J Gerontol Med Sci 2006 Comprehensive Geriatric Assessment, specialised care Reduced delirium severity and duration Flaherty JAGS 2003 Delirium RoomReduced mortality, Reduced use of sedating drugs Marcantonio JAGS 2010 Delirium Abatement Programme for post-acute care Improved detection of delirium by nursing staff

24 Nurse-led Multi-component intervention Real world trial, real nurses not research staff Recognition, treatment, prevention of complications, rehabilitation No improvement in delirium persistence at 2 weeks or 1 month Better detection Nurses found DAP challenging: competing priorities, insufficient time

25 Antipsychotics preferable to benzodiazepines Most evidence for haloperidol Atypical antipsychotics no better than haloperidol New trials of quetiapine and other atypicals on-going NICE has recommended trials to examine use of benzodiazepines, but most evidence indicates BZD increase risk and delirium duration Lacasse (2006), Cochrane Review : Lonergan (2009), Devlin (2010), Tahir (2010)

26 Guidelines Identify risk factors (age>65, cognitive impt, hip fracture, severe illness) and assess for delirium Tailored multi-component prevention programme Use CAM for diagnosis Distress: verbal de-escalation Distress: consider short course of low dose Haloperidol or Olanzapine Follow up and assess for possible dementia 1.Regular re-orientation, good lighting, clock, family 2.Adequate hydration 3.Adequate O2 saturation 4.Mobilise/walk regularly 5.Good pain control 6.Stop / reduce psychoactive drugs 7.Good nutrition 8.Provide glasses / hearing aids 9.Good sleep hygiene 10.Treat constipation, avoid catheters 11.Treat infections Tolerate & anticipate behaviour Be relaxed, unhurried and pleasant Be aware of non-verbal communication Don’t agitate, minimize stimulation Validation – respond to the feelings being expressed rather than the content Who, when, what, how – not why Diversion not confrontation Re-orientation sometimes Reasoning, arguing, shouting, admonition, threatening NEVER work

27 Distress: Haloperidol Haloperidol: use 0.5mg PO (max 4mg) Can repeat after 1-2 hours, usually bd or tds Oral liquid formulation is colourless and odourless aiding covert administration in a drink if required If very agitated: 1-2mg IM, repeated after 1 hour In older people ½-life can be >60 hours, and drug clearance can be 1-2 weeks Avoid in PD and Lewy Body Dementia

28 Distress: Olanzapine Olanzapine recommended by NICE as an alternative to haloperidol Use 2.5 mg oro-dispersible tablets, can repeat after 2 hours Can be placed on tongue or dispersed in water, apple juice, orange juice, milk or coffee Possibly fewer Parkinsonian side effects Sometimes more sedating than haloperidol

29 Distress: Lorazepam BGS guideline recommends for agitated delirium in PD and Lewy Body Dementia, or if anti-psychotics contra-indicated 0.5 – 1 mg PO, repeat after 2 hours if needed (max 3mg/24hours) 0.5 – 1 mg IV or IM, repeat after 2 hours if needed (dilute up to 2mls with N Saline, max 3 mg/24 hours)

30 Precipitating Factors infection, drugs, pain, environment, hypoxia, dehydration etc Delirium Impairment of consciousness Impaired attention Global cognitive impairment Sleep disturbance Protective factors IGF-1 ? Predisposing factors Age Neurodegeneration Frailty Sensory impairment Biology of delirium EP and imaging show involvement of subcortical & cortical structures

31 Neuro-inflammatory hypothesis: Systemic inflammation activates microglia already primed by age and neurodegeneration Neuro-transmitter hypothesis: Disturbance of cholinergic transmission exacerbated by drugs, infection, hypometabolism Neuro-endocrine hypothesis: ↓ Melatonin ↑ Cortisol Neuro-metabolism hypothesis: Reduced oxidative metabolism Changes in BBB permeability Cerebral electrolyte disturbance (↓Na) Toxic drug effects Biology of delirium

32 Adamis (2009) ↑ IFN-γ ↑ IL-6 ↑ IL-8 ApoE ε4 allele ↓ IGF-1 Predictors of delirium

33 Future delirium research Neuroprotection Increasing cerebral reserve Nutrition, drugs, orientation Biomarkers Imaging Intervention Trials Benzos, atypicals, melatonin, gabapentin, thiamine, hct Environmental research Delirium units Orientation aids Anti- inflammatory approaches cytokine blockade Anaesthesia Different types and depths of sedation


35 Summary Delirium is under-diagnosed Consider in the quiet, withdrawn patient Multi-component interventions are effective For severe agitation give haloperidol or olanzapine (lorazepam for PD/LBD) 1.Regular re-orientation, good lighting, clock, family 2.Adequate hydration 3.Adequate O2 saturation 4.Mobilise/walk regularly 5.Good pain control 6.Stop psychoactive drugs 7.Good nutrition 8.Provide glasses / hearing aids 9.Good sleep hygiene 10.Treat constipation, avoid catheters 11.Treat infections

36 Prof Clive Holmes (Southampton) Dr David Wilkinson (Southampton) Liz Sampson (UCL) Jugdeep Dhesi (Guy’s & St Thomas’ Hospital) Ed Marcantonio (Harvard Med School) Dr Jude Partridge (Maudsley) Jason Cross (Maudsley) Colm Cunningham (Dublin) ageing&health at southampton Please email any queries or questions to: Acknowledgements:

37 IL-1 IL-6 TNF-α Fever Malaise Depression Anorexia Delirium Fatigue Insomnia Sickness Behaviour: Induction of central cytokines, prostaglandins From Periphery to Brain

38 Systemic inflammation increases cognitive decline in Alzheimer’s disease Holmes et al. (2009)

39 ME7 mouse model of prion disease Mice have synaptic loss and neurodegeneration Primed microglia LPS used to mimic systemic infection T-maze task Systemic response the same


41 CQUIN CQUIN – Commissioning for Quality & Innovation payment framework Dementia Goal (2012/13): incentivise the identification of patients with dementia and to prompt appropriate referral and follow up Case finding in 90% of all patients 75+ admitted to hospital within 72 hours! 90% have further short diagnostic assessment & investigation 90% referred for specialist diagnosis & follow-up


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