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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.

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delirium and the relationship to anticholinergic burden

Delirium and The Relationship To Anticholinergic Burden

Miki Finnin, Pharm. D., BCPS, CGP

CEO/Pharmacist

Medication Advisors, PLLC

definition of delirium
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
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
Why Bother?
  • Common problem
  • Serious complications
  • Often unrecognized
  • May be preventable
prevalence in elderly
Prevalence in Elderly
  • Hospitalized 10 – 52%
  • Hospitalized with dementia 32 – 86%
  • Postoperative 15 – 53%
  • ICU 70 – 87%
  • NH/Post-acute care 20 – 60%
  • Palliative care up to 83%

Inouye S. N Engl J Med 2006; 354 :1157-65.

prevalence in elderly1
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.

slide8

http://www.uspharmacist.com/continuing_education/ceviewtest/lessonid/105762/http://www.uspharmacist.com/continuing_education/ceviewtest/lessonid/105762/

duration of delirium
Duration of Delirium
  • Transient phenomenon
  • May last weeks to months
vulnerability trigger interaction
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
Vulnerability Factors
  • Cognitive impairment
  • Depression
  • Alcohol abuse
  • Sensory deprivation
  • > 2 assisted ADL’s
  • Anticholinergic
  • Dehydration
  • Sodium abnormality
  • Vascular risk factors
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
    • Restraint use
    • Malnutrition
    • 3 new medications
    • Bladder catheterization
    • Any iatrogenic event
tipping point
Tipping Point
  • Patient had requested a sleep-aid because of insomnia and was given Tylenol PM
adverse drug events
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
Anticholinergic Burden
  • 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
Cumulative Anticholinergic Burden

Imipramine Cimetidine

Diphenhydramine Codeine

Ipratropium Coumadin

Amitryptilline Haldol

Quetiapine Alprazolam

Meclizine Nifedipine

Meperidine Prednisone

Paroxitine Lasix

Triamterene 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.

slide18

http://www.uspharmacist.com/continuing_education/ceviewtest/lessonid/105762/http://www.uspharmacist.com/continuing_education/ceviewtest/lessonid/105762/

common problem drugs
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 a1
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
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
Confusion Assessment Method (CAM) – Diagnostic Algorithm
  • Acute onset and fluctuating course
  • Inattention
  • Disorganized thinking
  • Altered level of consciousness
the cam instrument
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 instrument1
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 instrument2
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 instrument3
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 instrument4
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 instrument5
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
Causes of Delirium

44% of delirium is due to medications

Thus the TOP 3 causes of delirium are:

  • Medications
  • Medications
  • Medications
medical vs psychiatric
Medical Vs. Psychiatric

2/3 cases of delirium have an underlying medical cause and so a work-up must be initiated

assessment
Assessment
  • Vital signs
  • Examine the patient
  • UA
  • Cr, Na, K, Ca, Glu
  • CBC with diff
  • Meds review esp. Antichol, BDZ
  • Remove tethers
non pharmacological interventions
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
Treatment
  • Antipsychotics
  • Anticonvulsants
  • Benzodiazepines
a little evidence for pre op haldol
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.