1. Delirium: a Challenge in Prevention
Summer School of Neuroscience and Aging
Venice, Italy June, 2013
Richard W. Besdine, MD,FACP
Professor of Medicine
Greer Professor of Geriatric Medicine
Director, Division of Geriatrics and Palliative Medicine
Director, Center for Gerontology and Health Care Research
A L P E R T
M E D I C A L
S C H O O L

2. OBJECTIVES Know and understand: What is delirium?
How to recognize and diagnose delirium
Predisposing and precipitating risk factors
How to evaluate and treat elders with delirium
Interventions to prevent and treat delirium

3. Other Names for Delirium (AKA)
Acute confusional state
Acute mental status change
Altered mental status
Organic brain syndrome
Reversible dementia
Toxic or metabolic encephalopathy

4. Morbidity/Consequences of Delirium
A 10-fold risk of death in hospital
A 3-5 fold  risk of nosocomial complications, post- acute NH placement
↑ Length of stay, morbidity, mortality, costs
Poor functional recovery, mortality for 2 years
Acceleration of decline of dementia symptoms
Persistence of delirium, poor long-term outcomes
Decreased physical function
Institutionalization, prolonged rehabilitation
Delirium

5. Epidemiology, Detection of Delirium
1/3 of older patients presenting to the ED
1/3 of inpatients aged 70+ on general medical units, half of whom are delirious on admission
Under-recognition - nurses recognize, document < 50%; MDs recognize, document only 20%
DSM-IV criteria precise, difficult to apply
Confusion Assessment Method (CAM) performs better clinically: >95% sensitivity, specificity

6. Detecting Delirium Nurses recognize, document <50% of cases
Recognized by MDs
Recognized by nurses
Not recognized
Not recognized
Nurses recognize, document <50% of cases
Physicians recognize, document only 20%

7. DSM-IV Diagnostic Criteria
Disturbance of consciousness, reduced ability to focus, sustain, or shift attention
Change in cognition (e.g., memory, disorientation, language disturbance) or a perceptual disturbance not better accounted for by existing dementia
Develops quickly (hours to days) and fluctuates
Evidence from history, physical or labs of direct physiologic consequence of a medical condition
SOURCE: Data from the American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000;143.
Delirium

8. Confusion Assessment Method
Requires features 1 and 2, and either 3 or 4:
Acute change in mental status and fluctuating clinical course
Inattention by testing
Disorganized thinking
Altered level of consciousness

9. Varieties of Delirium
Hyperactive or agitated delirium - 25% of all cases
Hypoactive delirium - less recognized or appropriately treated
Mixed
Additional features include emotional symptoms, psychotic symptoms, “sundowning”

10. Neuropathophysiology: Cholinergic Deficiency Hypothesis
Acetylcholine is an important neurotransmitter for cognition
Delirium can be caused by anti-cholinergic drug overdose, and can be reversed by physostigmine
Delirium is associated with  serum anti- cholinergic activity
Anti-cholinergic activity is found in delirious patients taking no anti-cholinergic drugs

11. Neuropathophysiology: Inflammation
Especially important in postoperative, cancer and infected patients
Delirium associated with ↑ C-reactive protein, ↑ interleukin-1β, and ↑ tumor necrosis factor
Inflammation can break down blood-brain barrier, allowing toxic medications and cytokines access to CNS

12. Delirium as a Geriatrics Syndrome
Delirium, as with falls, is a result of the cumulative sum of predisposing (already present) and precipitating (new) factors
The more predisposing factors present, the fewer precipitating factors required to cause delirium, and vice versa
The more risk factors present, the more likely it is that delirium will occur
Intervening to modify or eliminate risk factors will reduce the likelihood of delirium

13. Relationship Between Predisposing and Precipitating Risk Factors
The chart demonstrates the interplay between predisposing or baseline risk factors and precipitating or hospital-related risk factors. Young healthy individuals with a low vulnerability will require a greater noxious insult to develop delirium whereas an older person with dementia, many comorbidities and sensory impairments will require a smaller insult, such as a UTI, to develop delirium.

14. Risk Factors for Delirium
Predisposing
Dementia
Co-morbidity
Sensory loss
Advanced Age
Functional loss
Malnutrition
Male, alcohol
Precipitating
Psychoactive Meds
Restraints, Catheter, Bed rest
Acute Illness
Fecal impaction, Retention
Surgery, Anesthesia
Pain
Sleep Deprivation
Sensory Deprivation
Fluid/electrolyte disorder
The chart demonstrates the interplay between predisposing or baseline risk factors and precipitating or hospital-related risk factors. Young healthy individuals with a low vulnerability will require a greater noxious insult to develop delirium whereas an older person with dementia, many comorbidities and sensory impairments will require a smaller insult, such as a UTI, to develop delirium.

15. Identification of Risk Factors
Initial Evaluation:
History, physical exam, vital signs
Targeted lab tests, search for infections
Review medications:
Prescription, PRN, OTC, herbal
Lower, stop or change any dangerous drugs
Further options:
Laboratory tests: thyroid, B12, drug levels, toxicology screen, ammonia, cortisol, ABG
Brain imaging, LP, EEG
Address all risks identified

16. One-Year Mortality of Delirium
919 patients enrolled in a delirium prevention intervention in 1995
100% follow-up one year following hospitalization with telephone interviews and review of death certificates
Those with delirium had ~50 days (0.13 of a year) of life lost, controlling for clinical covariates (p<0.001)
Leslie DL, Arch Int Med 2005;165:1657

17. Fitted Survival Curves With and Without Delirium
Survival Estimate
919 Discharged patients, 1year follow up;
delirious patients averaged 50 fewer days of life
Leslie DL, Arch Int Med 2005;165:1657

18. ___ Not delirious ED _ _ _ Delirious Discharge Survival Probability
Days
105 ED patients discharged, 30 with delirium. After adjusting for age, sex, function, cognition, co-morbid conditions and # meds, delirious patients were 7 times more likely to be dead at 6 months
Kakuma R et al..  JAGS 2003;51:443

19. Delirium Prevention Targets (High Risk)
Baseline cognitive impairment – orientation, avoid drugs, therapeutic activities
Sleep – non-pharmacologic intervention, environmental changes
Immobility – PT, maximum mobilization
Vision – aids (glasses, magnifiers), equipment (large print, touch pads)
Hearing – amplification, ear wax removal
Dehydration - early recognition, volume repletion
Inouye S, et al. NEJM 1999;340:

20. Delirium Prevention
Aim: reduce rate of incident delirium using a targeted multiple component intervention in high risk patients
Intervention: nurse/volunteer-based protocols for addressing identified risk factors in 852 medical in- patients aged >65,
Incident delirium reduced from 15% in control group to 9.9% in intervention group (34% risk reduction, P=0.02)
Hospital days reduced by one-third (P=0.02)
But delirium that did occur in intervention group was not attenuated
Inouye S, et al. NEJM 1999;340:

21. Intervention to Reduce Delirium
Inouye S, et al. NEJM 1999;340:

22. Management – No Drugs Adequate stimulation – hearing, vision
Mobility – avoid bed rest, mobilize ASAP, avoid restraints (including catheters)
Vision and hearing
Nutrition – dentures, feeding help
Orientation - day, time, place, people, tests
Sleep hygiene

23. No-Drug Sleep Protocol
Warm drink, relaxing music, quiet dark room, back rub, minimize awakenings
Quality of sleep correlated with the # of parts of the protocol received
Decreased sedative use from 54% to 31%
Sleep protocol had a higher association with quality of sleep than a sedative
Not as effective in chronic users of sedatives
McDowell et al. JAGS 1998;46:700

24. Guideline for Delirium Prevention
Assessment and modification of key clinical factors
that may precipitate delirium, including
Cognitive impairment
Dehydration
Constipation
Hypoxia
Infection
Immobility
Limited mobility
Multiple medications
Pain
Poor nutrition
Sensory impairment
Sleep disturbance
O'Mahony R et al. Ann Intern Med. 2011;154:746-51

25. Management - Drugs Drugs increase severity and duration of delirium
All neuroleptics produce extrapyramidal disorders, over-sedation, increased risk of stroke and death
Haloperidol only drug in randomized trials that was better than others (or better than placebo) in reducing dangerous behavior
If severe agitation is a danger to self or others, or interferes with essential therapy, haloperidol, mg IV/PO every 30 minutes until sedated (max 3-5mg/24 hours), then ½ loading dose each 24 hours in divided doses – taper in DAYS

26. Pharmacologic Treatment of Delirium
Table 4. Pharmacologic Treatment of Delirium.
Inouye S. N Engl J Med 2006;354:

27. Post-Operative Delirium1

28. Post-Operative Delirium2
Pre-operative risk factors:
Age 70 and older
Cognitive impairment
Physical functional impairment
History of alcohol abuse
Abnormal serum chemistries
Intra-thoracic or aortic aneurysm surgery

29. Summary Delirium is common, major morbidity for older persons
High sensitivity and specificity for detection by CAM
Careful Hx, PE, focused labs will detect cause
Careful medication review mandatory; D/C possible contributory agents
Managing delirium requires Rx of primary disease, avoiding complications, managing behavioral problems, providing rehabilitation
The best treatment for delirium is prevention

30. Case 11
A 72-year-old man is evaluated because nurses are concerned about his agitation, which increases markedly in the evenings
He underwent emergency hip replacement 3 days ago after he fell and fractured his hip
He gets antipsychotic agents to control agitation at night; he yells “help me” constantly, and is determined to get out of bed alone and walk
In the year before his fall, he had stopped working and driving, but we don’t know why

31. Case 12
The patient’s history includes hypertension, benign prostatic hyperplasia, and osteoarthritis; there is no history of dementia
On examination, he appears confused and is disoriented to place and time
He has some pain with hip movement
Neurologic examination reveals no focal abnormalities

32. Case 13
Which of the following is most helpful in establishing the diagnosis of delirium?
Order electrolytes, BUN, glucose, and thyrotropin
Determine why the patient stopped working and driving
Perform the digit-span memory test
Order CT of the brain
Review the patient’s medication list

33. DSM-IV Diagnostic Criteria
Disturbance of consciousness, reduced ability to focus, sustain, or shift attention
Change in cognition (e.g., memory, disorientation, language disturbance) or a perceptual disturbance not better accounted for by existing dementia
Develops quickly (hours to days) and fluctuates
Evidence from history, physical or labs of direct physiologic consequence of a medical condition
SOURCE: Data from the American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000;143.
Delirium

34. Confusion Assessment Method
Requires features 1 and 2, and either 3 or 4:
Acute change in mental status and fluctuating clinical course
Inattention by testing
Disorganized thinking
Altered level of consciousness

35. Case 14
Which of the following is most helpful in establishing the diagnosis of delirium?
Order electrolytes, BUN, glucose, and thyrotropin
Determine why the patient stopped working and driving
Perform the digit-span memory test
Order CT of the brain
Review the patient’s medication list

36. Case 21
An 89-year-old man is admitted to a nursing home for rehabilitation after being hospitalized for pneumonia; he is anxious and fidgety
He is widowed and lives in the community
History includes hypertension, benign prostatic hyperplasia, major depressive disorder and chronic back pain
Medications on transfer to the nursing home include metoprolol, oxybutynin, paroxetine, acetaminophen with codeine and amitriptyline

37. Case 22
Which of the following medications is least likely to contribute to delirium?
Amitriptyline
Acetaminophen with codeine
Oxybutynin
Paroxetine
Metoprolol

38. Case 22
Which of the following medications is least likely to contribute to delirium?
Amitriptyline
Acetaminophen with codeine
Oxybutynin
Paroxetine
Metoprolol

39. Case 31
A 90-year-old man is brought to the emergency department by his family because he has had an abrupt change in behavior
The patient moved into his daughter and son-in-law’s house a few months ago, because he was no longer able to manage living alone
A few days ago he became aggressive and angry, and hit his son-in-law for no apparent reason
He has also become incontinent in the last 2 days

40. Case 32
He has multiple bruises, which the family suspects are from falling
The patient’s history includes moderate dementia and benign prostatic hyperplasia
Blood pressure is 160/90 mmHg; all other vital signs are normal, and the physical exam is unremarkable
He is demanding to be released from “prison” and is aggressive with the staff
He is uncooperative with the neurologic exam, but he appears to be moving all extremities well

41. Case 33 What is the most appropriate next step? Bladder scan
Lumbar puncture
Electroencephalography
CT of the brain
Basic metabolic panel, CBC, and pulse oximetry

42. Case 33 What is the most appropriate next step? Bladder scan
Lumbar puncture
Electroencephalography
CT of the brain
Basic metabolic panel, CBC, and pulse oximetry