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Delirium and The Relationship To
Anticholinergic Burden
Miki Finnin, Pharm. D., BCPS, CGP
CEO/Pharmacist
Medication Advisors, PLLC
Definition of Delirium
• A disturbance in consciousness with reduced
ability to focus, sustain or shift attention that
occurs over a short period of time and tends
to fluctuate over the course of a day
• Acute brain failure
• Evidence of an underlying general medical
condition
Case “A”
You are the overnight provider and are called by the nurse to
evaluate “Mrs. A” who has pulled out her IV and is insisting on
leaving the hospital because “nothing is being done”.
A quick review of the chart shows:
• 100 yr old lady with h/o CAD, CHF, DM, GERD, urinary
incontinence and depression admitted for CHF exacerbation
secondary to non compliance
• Meds – ASA, beta blocker, ACEI, nifedipine, lasix, KCL,
oxybutinin, cimetidine, paroxitine
Why Bother?
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Common problem
Serious complications
Often unrecognized
May be preventable
Prevalence in Elderly
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Hospitalized
Hospitalized with dementia
Postoperative
ICU
NH/Post-acute care
Palliative care
Inouye S. N Engl J Med 2006; 354 :1157-65.
10 – 52%
32 – 86%
15 – 53%
70 – 87%
20 – 60%
up to 83%
Prevalence in Elderly
• Complicates more than 2.3 million
hospitalized older adults annually
• Associated with 17.5 million hospital days
• > 4 billion in excess annual health care
expenditures
Inouye S. Am J Med 1994; 97(3) : 278-88.
Rizzo, et al. Medical Care 2001; 39(7):740.
http://www.uspharmacist.co
m/continuing_education/cevi
ewtest/lessonid/105762/
Duration of Delirium
• Transient phenomenon
• May last weeks to months
Vulnerability-Trigger Interaction
• Complex interaction among various degrees of
insult and different levels of patient
vulnerability
• Hence the wide range of prevalence 10 -86%
Vulnerability Factors
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Cognitive impairment
Depression
Alcohol abuse
Sensory deprivation
> 2 assisted ADL’s
Anticholinergic
Dehydration
Sodium abnormality
Vascular risk factors
Risk Factors
• Intrinsic Factors
– Vision impairment
(<20/70)
– Cognitive impairment
(MMSE < 24)
– Severe illness
(APACHEII > 16)
– BUN/CR ratio > 18
Inouye S, et al. JAMA 1996; 275(11):852-7.
• Precipitating Factors
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Restraint use
Malnutrition
3 new medications
Bladder catheterization
Any iatrogenic event
Tipping Point
• Patient had requested a sleep-aid because of
insomnia and was given Tylenol PM
Adverse Drug Events
• Potential for interaction
– 2 drugs
6%
– 5 drugs
50%
– > 6 drugs
nearly 100%
• 70 – 80% of adverse drug events in the elderly
are dose related
• 30 – 50% are preventable
Carbonin P, et al. JAGS 1991; 39:1093-99.
Anticholinergic Burden
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Drugs with no anticholinergic effects were rated “0”
Mildly anticholinergic drugs were scored as “1”
Moderately anticholinergic drugs were rated “2”
Highly anticholinergic drugs were scored as “3”
Rudolph JL, et al. Arch Intern Med 2008; 168(5):508-13.
Cumulative Anticholinergic Burden
Imipramine
Diphenhydramine
Ipratropium
Amitryptilline
Quetiapine
Meclizine
Meperidine
Paroxitine
Triamterene
Cimetidine
Codeine
Coumadin
Haldol
Alprazolam
Nifedipine
Prednisone
Lasix
Digoxin
Han L, et al. J Am Geriatr Soc 2008; 56(12):2203-10.
Rudolph JL, et al. Arch Intern Med 2008; 168(5):508-13.
Medications Associated with Delirium
High-Risk Medications
Low-Risk Medications
Analgesics
NSAIDs, opioids
Cardiovascular agents
Antiarrhythmics, beta-blockers, clonidine, digoxin
Anticholinergics
Atropine, benztropine,
diphenhydramine,
scopolamine
Antimicrobials
Acyclovir, aminoglycosides, amphotericin B,
cephalosporins, fluoroquinolones, linezolid,
macrolides, penicillin, sulfonamides
Antidepressants
Mirtazapine, SSRIs, TCAs
Anticonvulsants
Carbamazepine, phenytoin, valproate
Sedative-hypnotics
Benzodiazepines, propofol
Gastrointestinal agents
Antiemetics, H2 -receptor antagonists
Corticosteroids
Hydrocortisone, prednisone,
methylprednisone, dexamethasone
Skeletal muscle relaxants
Baclofen
Dopamine agonists
Amantadine, bromocriptine, levodopa,
pergolide, pramipexole, ropinirole
http://www.uspharmacist.com/continuing_edu
cation/ceviewtest/lessonid/105762/
Common Problem Drugs
• Anticholinergic medications increase delirium risk
• Diphenhydramine
– Odd ration (OR) of catheter placement 2.5
– OR delirium 1.8
• Psychoactive medications increase ADEs
• Non-steroidals, cardiac medications
Agostini JV, et al. Arch Intern Med 2001; 161:2091-7.
Han L, et al. Arch Intern Med 2001; 161:1099-105.
Case “A”
You are the overnight provider and are called by the nurse to
evaluate “Mrs. A” who has pulled out her IV and is insisting on
leaving the hospital because “nothing is being done”.
A quick review of the chart shows:
• 100 yr old lady with h/o CAD, CHF, DM, GERD, urinary
incontinence and depression admitted for CHF exacerbation
secondary to non compliance
• Meds – ASA, beta blocker, ACEI, nifedipine, lasix, KCL,
oxybutinin, cimetidine, paroxitine, Tylenol PM
Recognition of Delirium
• RN’s recognize only 50% of cases
• MD’s recognize only 20% of cases
Classic Presentation
wildly agitated patient
presents in only 25% of cases
Confusion Assessment Method (CAM) –
Diagnostic Algorithm
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Acute onset and fluctuating course
Inattention
Disorganized thinking
Altered level of consciousness
The CAM Instrument
1. [Acute Onset] Is there evidence of an acute change in mental
status from the patient’s baseline?
2A. [Inattention] Did the patient have difficulty focusing attention,
for example, being easily distractible, or having difficult
keeping track of what was being said?
2B. (If present or abnormal) Did this behavior fluctuate during the
interview, that is, tend to come and go or increase and
decrease in severity?
3. [Disorganized thinking] Was the patient’s thinking disorganized or
incoherent, such as rambling or irrelevant conversation,
unclear or illogical flow of ideas, or unpredictable switching from
subject to subject?
The CAM Instrument
4. [Altered level of consciousness] . Overall, how would you rate this
patient’s level of consciousness? (Alert [normal];
Vigilant [hyperalert, overly sensitive to environmental stimuli,
startled very easily], Lethargic [drowsy, easily aroused];
Stupor [difficult to arouse]; Coma; [unarousable]; Uncertain)
5. [Disorientation] Was the patient disoriented at any time during the
interview, such as thinking that he or she was
somewhere other than the hospital, using the wrong bed, or
misjudging the time of day?
6. [Memory impairment] Did the patient demonstrate any memory
problems during the interview, such as inability to
remember events in the hospital or difficulty remembering
instructions?
The CAM Instrument
7. [Perceptual disturbances] Did the patient have any evidence of
perceptual disturbances, for example, hallucinations,
illusions or misinterpretations (such as thinking something was
moving when it was not)?
8A. [Psychomotor agitation] At any time during the interview did the
patient have an unusually increased level of motor
activity such as restlessness, picking at bedclothes, tapping fingers
or making frequent sudden changes of position?
8B. [Psychomotor retardation]. At any time during the interview did
the patient have an unusually decreased level of motor
activity such as sluggishness, staring into space, staying in one
position for a long time or moving very slowly?
9. [Altered sleep-wake cycle]. Did the patient have evidence of
disturbance of the sleep-wake cycle, such as excessive daytime
sleepiness with insomnia at night?
The CAM Instrument
Feature 1: Acute Onset or Fluctuating Course
This feature is usually obtained from a family member or nurse and is
shown by positive responses to the following questions:
Is there evidence of an acute change in mental status from the
patient’s baseline? Did the (abnormal) behavior fluctuate during the
day, that is, tend to come and go, or increase and decrease in
severity?
Feature 2: Inattention
This feature is shown by a positive response to the following question:
Did the patient have difficulty focusing attention, for example,
being easily distractible, or having difficulty keeping track of what
was being said?
The CAM Instrument
Feature 3: Disorganized thinking
This feature is shown by a positive response to the following question:
Was the patient’s thinking disorganized or incoherent, such as
rambling or irrelevant conversation, unclear or illogical flow of
ideas, or unpredictable switching from subject to subject?
Feature 4: Altered Level of consciousness
This feature is shown by any answer other than “alert” to the following
question:
Overall, how would you rate this patient’s level of consciousness?
(alert [normal]), vigilant [hyperalert], lethargic [drowsy, easily
aroused], stupor [difficult to arouse], or coma [unarousable])?
• The diagnosis of delirium by CAM requires the presence of
features 1 and 2 and either 3 or 4.
The CAM Instrument
• Sensitivity of 94%
(95% CI = 91 – 97%)
• Specificity of 89%
(95% CI = 85 – 94%)
Wei L, et al. JAGS 2008; 56(5):823-30.
Causes of Delirium
44% of delirium is due to medications
Thus the TOP 3 causes of delirium are:
• Medications
• Medications
• Medications
Diagnosis
Medical Vs. Psychiatric
2/3 cases of delirium have an underlying
medical cause and so a work-up must be
initiated
Assessment
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Vital signs
Examine the patient
UA
Cr, Na, K, Ca, Glu
CBC with diff
Meds review esp. Antichol, BDZ
Remove tethers
Non-Pharmacological Interventions
• Pacing – allow to pace as long as safe
• Social isolation – talk to the agitated patient to
distract them
• Night-lite to orient
• Keep daytime light as bright as possible
• Pet therapy
• 1:1 observation – have family visit and stay with
patient
Treatment
• Antipsychotics
• Anticonvulsants
• Benzodiazepines
A Little Evidence for Pre-Op Haldol
• 430 hip fracture patients aged 70+ at risk for post-op
delirium
– Visual impairment
– APACHE II >16
– MMSE < 25
– BUN/Cr > 18
• Randomized to receive haloperidol 1.5 mg daily started
pre-op and continued until 3 days post surgery
Kalisvaart K, et al. JAGS 2005; 53:1658-66.
Results
Haloperidol
Placebo
P value
Delirium Incidence
15.1%
16.5%
NS
Delirium Severity
14.4
18.4
<0.001
Delirium Duration
5.4 days
11.8 days
< 0.001
Hospital Days
17.1
22.6
< 0.001