Delirium

1. Delirium Dr Dan Wilson Consultant Geriatrician, Kings College Hospital, London

3. Introduction • Transient global disorder of cognition • Primarily disorder of attention • Acute onset, reversible and preventable • Poor outcomes (morbid and mortal) • Expensive (half of inpatient bed days in US) • Should be regarded as a medical emergency

4. DSM5 criteria • Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment) • Disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day • Additional disturbance in cognition (e.g. memory deficit, disorientation, language, visuospatial ability, or perception) • Disturbances in Criteria (a) and (c) are not better explained by a pre-existing, established or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma • There is evidence from the history, physical examination or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal, or exposure to a toxin, or is due to multiple etiologies.

5. Common features • Combative or very withdrawn • Profound disorientation • Visual hallucinations • Delusions • Disorganised thinking • Sleep-wake cycle disturbance

6. Where is delirium? • 1-2% community prevalence (14% over 85) • Incidence up to 60% care home residents • Prevalent 14-24% all admissions • Further 6-56% develop on wards • Detectable in up to 42% #NOF patients at day 3 post-op • Up to 87% ITU admissions affected • 83% of terminally ill patients • Unrecorded in 50% of medical records • Inouye N Eng J Med 2006 • Young et al Age and Ageing 2003

7. Who gets delirium? • Age • Pre-existing dementia/ cognitive impairment • Multiple co-morbidities/ severe illness • Poly-pharmacy • Sensory impairment • Hip # • (Education and Fitness possibly protect?)

8. What causes delirium? • Medical causes • Anything? • Other precipitants • Use of Physical Restraints (4.4) • Malnutrition (4.0) • Addition of three or more medications (2.9) • Catheterisation (2.4) • Iatrogenic events (1.9) Inouye et al JAMA 1996

9. Risk of delirium: model Inouye SK, Charpentier PA JAMA 1996

11. Pathophysiology • Direct brain insult • Energy deprivation • Metabolic derangement • CNS trauma • Infection • Tumour • Drugs • Aberrant stress response • Limbic-HPA axis • Sympathetic drive • Systemic inflammation

12. Cortisol • Steroid psychosis • Cognitive dysfunction in Cushing’s • High levels in severe illness • Exaggerated in older, demented and multi-morbid • Higher in delirious hip fracture CSF • Reduced odds in GR receptor haplotype

13. Inflammation • Serum IL-6 and IL-8 elevated • Elderly hip fracture • IFNγ (pro-inflammatory) and IL-RA and IGF-1 (anti-inflammatory) levels also altered • Elderly medical • CSF IL-8 elevated • Hip fracture

14. Adaptive sickness behaviour (rodents) Cunningham C, MacLullich A

15. Exaggeration of sickness behaviour? • Severe illness • Septic encephalopathy • Persisting deficits • Susceptible individuals • Microglial priming • Exaggerated IL-1B response

16. Maladaptation Cunningham C, MacLullich A

17. Final common pathway? • Unclear • Cholinergic deficiency? • Dopamine excess? • NA excess? • GABA excess? • All?

19. Enough to make you delirious? “acute confusional state” “toxic psychosis” “ICU psychosis” “post-operative psychosis” “metabolic encephalopathy” “acute brain failure” “organic brain syndrome” “cerebral insufficiency” “dysergastic reaction” “acute dementia/depression” “a bit muddled” “not themselves” “confused” “agitated” “a bit knocked off” “vague” “poor historian” “non-compliant” “obtunded” “flat”

20. DSM5 criteria • Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment) • Disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day • Additional disturbance in cognition (e.g. memory deficit, disorientation, language, visuospatial ability, or perception) • Disturbances in Criteria (a) and (c) are not better explained by a pre-existing, established or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma • There is evidence from the history, physical examination or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal, or exposure to a toxin, or is due to multiple etiologies.

21. CAM • Based on DSM III-R • Semi-structured approach • Attention test • Collateral • Condensed to four key features • 1)Acute onset and fluctuating course • 2)Inattention • 3)Disorganized thinking • 4)Altered level of consciousness • (1 + 2) +3 and/or 4 diagnose delirium • Inouye et al Annals Int Med 1990

22. DRS-R-98 • Measured against dementia, depression, schizophrenia • 16 items • 3 diagnostic; 13 rate severity • Allows measurement of change over time • Cumbersome, but useful for research? Trzepacz J Neuropsychiatry Clin Neurosci 2001

23. www.the4at.com

25. Prognosis • Inpatient mortality 22-76% • One year mortality 35-40% • 60% resolve in 6 days • 5% delirious >1 month • 38% >=1 symptom still at discharge • Higher rates of complications and institutionalisation • Accelerated cognitive decline

26. Delirium predicts decline in MMSE 30 30 25 25 20 20 No delirium MMSE 15 15 10 10 Delirium 5 5 0 0 Years in study 0 2 4 6 8 10 Davis et al, Brain 2012

27. Memory decline in AD Fong et al, Neurology 2009

29. Treatment • Identify primary and secondary causes • Optimise physiology • Manage pain/bladder/bowels • Nutrition/hydration • Environment

30. Common primary causes • Infection • Pharmacological • Metabolic/Renal/Electrolyte/Hepatic • Cardiopulmonary (hypoxic/hypercapnoeic) • Stroke/trauma • Alcohol withdrawal

31. Unusual primary causes • Wernicke’s • Endocrinopathies • Para-neoplastic/autoimmune encephalopathy • Vasculitides • Accelerated hypertension

32. Differentials • Non-convulsive status • Psychosis • Behavioural disturbance in dementia • DLB

33. Drugs • Reduce cholinergic burden • Address pain • Sedation • Specific treatments? • BZD’s for withdrawal states • Antipsychotics? • Cholinesterase inhibitors may harm • Melatonin no effect

34. Environment • Orientating • Calm • Well lit • Consistent nursing • Early therapy • Ward moves?

36. Hospital Elder Life Program • Cognition • Orientation • Exercise • Sensory • Sleep • Resource intense; cost effective (in USA) • 30% reduction Inouye et al, N Eng J Med 1999

37. Proactive Geriatric Consultation • Structured management protocol in Orthopaedics • 10 areas (medical and nursing) • Max 5 recommendations • 3 on follow up • 36% reduction delirium • >50% reduction severe delirium Marcantonio et al, JAGS, 2001

38. Drugs for prevention • Haloperidol in emergency hip surgery • Olanzapine in elective knee and hip surgery Kalisvaart et al, JAGS 2005 Larsen et al, Psychosomatics 2010

39. Summary • Common serious under-detected • Risks and sequelae are understood • Preventable • Can reduce severity and duration • Proven treatment and prevention not adopted • Pathophysiology still not well understood • Lack good drug trials • Promote better follow up to detect dementia

40. Reading • Subjective experience of a Confusional State. JL Crammer (Br J Psych) 2002, 180, 71-75 • Delirium In Older Persons. S Inouye (NEJM) 2006; 354:1157-65 • Journal of Psychosomatic Research 65 (2008) • www.europeandeliriumassociation.com • http://elderlife.med.yale.edu/public/public-main.php • NICE Guidelines

41. Thankyou