delirium: a challenge in prevention summer school of neuroscience and aging venice, italy 10-14...

Delirium: a Challenge in Prevention

Summer School of Neuroscience and Aging Venice, Italy 10-14 June, 2013

Richard W. Besdine, MD,FACPProfessor of Medicine

Greer Professor of Geriatric MedicineDirector, 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

OBJECTIVES

Know and understand:What is delirium?How to recognize and diagnose deliriumPredisposing and precipitating risk factorsHow to evaluate and treat elders with

deliriumInterventions to prevent and treat delirium

Other Names for Delirium (AKA)

Acute confusional state Acute mental status change Altered mental status Organic brain syndrome Reversible dementia Toxic or metabolic encephalopathy

A 10-fold risk of death in hospitalA 3-5 fold risk of nosocomial complications, post-

acute NH placement↑ Length of stay, morbidity, mortality, costsPoor functional recovery, mortality for 2 yearsAcceleration of decline of dementia symptomsPersistence of delirium, poor long-term outcomesDecreased physical function Institutionalization, prolonged rehabilitation

Morbidity/Consequences of Delirium

Epidemiology, Detection of Delirium

1/3 of older patients presenting to the ED1/3 of inpatients aged 70+ on general medical

units, half of whom are delirious on admissionUnder-recognition - nurses recognize, document

< 50%; MDs recognize, document only 20%DSM-IV criteria precise, difficult to applyConfusion Assessment Method (CAM) performs

better clinically: >95% sensitivity, specificity

Detecting Delirium

Nurses recognize, document <50% of cases Physicians recognize, document only 20%

Recognized by MDs Recognized

by nurses

Not recognized Not recognized

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 fluctuatesEvidence from history, physical or labs of direct

physiologic consequence of a medical condition

Confusion Assessment Method Requires features 1 and 2, and either 3 or 4:

1. Acute change in mental status and fluctuating clinical course

2. Inattention by testing

3. Disorganized thinking

4. Altered level of consciousness

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”

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

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

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

Relationship Between Predisposing and Precipitating Risk Factors

Risk Factors for Delirium

Predisposing

DementiaCo-morbiditySensory lossAdvanced AgeFunctional lossMalnutritionMale, alcohol

Precipitating

Psychoactive MedsRestraints, Catheter, Bed restAcute IllnessFecal impaction, RetentionSurgery, AnesthesiaPainSleep DeprivationSensory DeprivationFluid/electrolyte disorder

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, EEGAddress all risks identified

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

Leslie DL, Arch Int Med 2005;165:1657

Fitted Survival Curves With and Without DeliriumS

urv

ival

Est

ima

te

919 Discharged patients, 1year follow up;delirious patients averaged 50 fewer days of life

ED___ Not delirious_ _ _ Delirious

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

Sur

viva

l Pro

babi

lity

Days

Discharge

Delirium Prevention Targets (High Risk)

Baseline cognitive impairment – orientation, avoid drugs, therapeutic activities

Sleep – non-pharmacologic intervention, environmental changes

Immobility – PT, maximum mobilizationVision – aids (glasses, magnifiers), equipment

(large print, touch pads)Hearing – amplification, ear wax removalDehydration - early recognition, volume repletion

Inouye S, et al. NEJM 1999;340:669-676

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, 1995-98

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


Intervention to Reduce Delirium


Management – No Drugs

Adequate stimulation – hearing, visionMobility – avoid bed rest, mobilize ASAP,

avoid restraints (including catheters)Vision and hearingNutrition – dentures, feeding helpOrientation - day, time, place, people, testsSleep hygiene

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

Cognitive impairmentDehydrationConstipationHypoxia Infection Immobility

Guideline for Delirium Prevention

Limited mobility Multiple medications Pain Poor nutrition Sensory impairment Sleep disturbance

Assessment and modification of key clinical factorsthat may precipitate delirium, including

O'Mahony R et al. Ann Intern Med. 2011;154:746-51

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, 0.25-1.0mg 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

Inouye S. N Engl J Med 2006;354:1157-1165

Pharmacologic Treatment of Delirium

Post-Operative Delirium1

15%

50% 50%

Electivenoncardiac

surgery

Cardiac surgery,AAA repair

surgery

Hip fracturerepair

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

No pre-op risk factors

1 or 2 pre-op risk fac-

tors

3+ pre-op risk factors

2%10%

50%

Post-Operative Delirium2

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

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

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

Case 12

Which of the following is most helpful in establishing the diagnosis of delirium?

A. Order electrolytes, BUN, glucose, and thyrotropin

B. Determine why the patient stopped working and driving

C. Perform the digit-span memory test

D. Order CT of the brain

E. Review the patient’s medication list

Case 13

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 fluctuatesEvidence from history, physical or labs of direct

physiologic consequence of a medical condition

Confusion Assessment Method Requires features 1 and 2, and either 3 or 4:

1. Acute change in mental status and fluctuating clinical course

2. Inattention by testing

3. Disorganized thinking

4. Altered level of consciousness

Which of the following is most helpful in establishing the diagnosis of delirium?

A. Order electrolytes, BUN, glucose, and thyrotropin

B. Determine why the patient stopped working and driving

C. Perform the digit-span memory test

D. Order CT of the brain

E. Review the patient’s medication list

Case 14

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

Which of the following medications is least likely to contribute to delirium?

A. Amitriptyline

B. Acetaminophen with codeine

C. Oxybutynin

D. Paroxetine

E. Metoprolol

Case 22

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

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

Case 32

What is the most appropriate next step?

A. Bladder scan

B. Lumbar puncture

C. Electroencephalography

D. CT of the brain

E. Basic metabolic panel, CBC, and pulse oximetry

Case 33

delirium: a challenge in prevention summer school of neuroscience and aging venice, italy 10-14...

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