Altered Mental Status - Dallas Area Gerontological Society

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					Let’s be clear about Delirium
  Dallas Area Gerontological

         October 18, 2012
         Vivyenne Roche MD
Aurelianus    First described the syndrome
Hippocrates   Disease denoting a mental
 5 BC          disorder & serious illness
              Differentiation from
              conventional madness
              “phrenitis, lethargus”
Celsus        de lira -off the path
 1 AD
Van Swieten   Last used the term phrenitis,
  1700-72     descriptive term, no causal
              relationship, inflammation of
              the diaphragm, combination
              of mental disorder with fever
Morgagni      Delirium replaced phrenitis
1980          DSM III criteria by the APA
Delirium - ? Prevalence
• Point prevalence 1.1% for adults > 55 yrs.
• 2.3 million elderly hospitalized patients/yr
• Probably the most frequent complication of
  hospitalization in the elderly
• Incidence on admission 10-25% (40%)
• 5-35% (50%) may develop it in hospital
• 14-56% of pts. on general medical wards
Delirium - ? Prevalence
High occurrence in postoperative patients
     General sx                  10-15%
     Orthopedic sx               28-61%
     Cataract sx                 1-3%
Fem. neck fx./bil. knee replace. 65%

Nursing home patients > 75 yrs. 60%
Terminal delirium               25-85%
Delirium - Importance
• Predictor of poor prognosis
• In hospitalized patients 2 to 20 times higher
  mortality rates in patients with delirium than
  those without it
• Case fatality rates 25% to 35%
• Closer nursing surveillance
• Higher hospital costs per day
Delirium - Importance
• Longer hospital length of stay (LOS);
  Hospital LOS increased by 60%
• Reduce delirium LOS by one day:
  save $1-2 billion dollars/year
• Lasts hours, weeks, or months;
  18% of patients had delirium at 6 months
• 5 times higher nursing home placement,
  increased home care and rehabilitation use
Delirium -Pathophysiology
Physiology of Normal Aging:
• Cerebral blood flow declines by 28%
• Neuronal Loss
• Lower amounts of acetylcholine, dopamine,
  GABA and norepinephrine
• Loss of release of neurotransmitters and reduction
  in receptor function

            Less physiologic reserve
Delirium -Pathophysiology
Neuroanatomical location:
     Prefrontal cortex (TBI, cirrhotics)
     Thalamus (CVAs)
     Posterior parietal cortex (CVAs)
     Fusiform cortex (CVAs)
     Basal ganglia (ECT-induced delirium)
Delirium -Pathophysiology
Multiple neurotransmitters systems include
 serotonergic, GABA-ergic, noradrenergic,
 glutaminergic and histaminergic involved
Neurotransmitters mediate delirium and are
 potential targets for treatment
Acetylcholine deficiency/dopamine excess
Delirium -Pathophysiology
• Cholinergic function is critical for normal
• Administration of anticholinergics produce
  clinical delirium with typical EEG changes
• Acetylcholine synthesis is decreased in
  cerebral hypoxia and hypoglycemia
• Increased cerebral dopamine levels can cause
  delirium and dopamine inhibitors such as
  haloperidol can reduce anticholinergic and
  dopaminergic mediated delirium
Delirium -Pathophysiology
• Opiates known to cause delirium:
  they increase the activity of dopamine
  and decrease acetylcholine activity
• Several commonly prescribed drugs for older
  people possess anticholinergic properties:
  Furosemide (0.22), Digoxin (0.25),
  Cimetidine (0.86), Prednisolone (0.55),
  Warfarin (0.12), Theophylline (0.44).
Delirium -Pathophysiology
• Serotonin is the most abundant neurotransmitter in
  the brainstem; its synthesis and release depends on its
  precursor tryptophan
• Cerebral serotonin is increased in hepatic
  encephalopathy, septic delirium, and in the serotonin
  syndrome. Alcohol withdrawal, L DOPA-induced
  delirium and postoperative delirium have been
  associated with decreases in tryptophan
• Serotonin syndrome related to combination of SSRIs
  and MAOIs or TCAs. Restlessness, tremor,
  hyperpyrexia, myoclonus, nausea, flushing and one of
  its main symptoms is delirium
Delirium -Pathophysiology
• Gamma-aminobutyric acid (GABA) is the
  predominant inhibitory neurotransmitter in the CNS
• In hepatic encephalopathy there is increased ammonia
  levels, precursor of GABA. Benzodiazepine and
  alcohol withdrawal are associated with reduced
  GABA activity
• Cytokines, TNF alpha, interleukin-1, interleukin-2
  normally found in low levels in the CNS but increase
  after stress, infection, inflammation, and trauma. This
  leads to HPA axis activation, increased permeability
  of the blood brain barrier and interference with
  neurotransmitter synthesis and transmission.
Proposed Mechanisms of Delirium and Possible Associated Clinical Conditions
                              Medications                  Medications/Medical Illness
                              Alcohol withdrawal           Surgical Illness

                                                                          Benzodiazepine and
               Medications                                                Alcohol Withdrawal
               Stroke            Cholinergic         Cholinergic
                                  activation         Inhibition
                        Dopamine                                     Reduced
                        Activation                                   GABA Activity
                Cytokine                                          GABA               Benzodiazepines
                Excess                                            Activation         Hepatic Failure
                        Activation                               Glutamate

                Medications             Serotonin         Cortisol
                                                                                 Hepatic failure
            Substance withdrawal
                                        Deficiency        Excess               Alcohol withdrawal

                                    Tryptophan depletion               Glucocorticoids
                                    Phenylalanine elevation          Cushings Syndrome
                             Surgical Illness /Medical Illness
Ancient Greeks: syndrome that accompanied
      fever or other serious illness:
      phrenitis (frenzy); lethargus (lethargy)
• Hyperactive presentation (hallucinations,
  agitation, inappropriate behavior)
• Hypoactive presentation (hypersomnolence,
  lethargy-may present like depression)
• Mixed-features of both
Delirium Subtypes of delirium
• Hyperactive (22%-30%) hypoactive (24%-26%)
  and mixed (42%-46%)
• Comparable deficits in cognition with both
• Hyperactive delirium occurs in benzodiazepine
  withdrawal, renal or hepatic encephalopathy often
  present with hypoactive delirium
• There is no exclusive relationship between
  subtypes of delirium and different etiologies
• Hypoactive pts: sicker on admission, longest
  lengths of stay, inc. pressure sores whereas the
  hyperactive pts. are more likely to fall
Delirium - Diagnosis
DSM IV Criteria
Disturbance of consciousness (i.e., reduced
 clarity of awareness of the environment)
 with reduced ability to focus, sustain or shift
Change in cognition (such as memory deficit,
 disorientation, language disturbance) or the
 development of a perceptual disturbance
Delirium - Diagnosis
DSM IV Criteria
Disturbance that develops over a short period
 of time (usually hours to days) and tends to
 fluctuate over the course of the day
Evidence from history, physical examination,
 or laboratory findings that the disturbance is
 caused by a specific medical condition
 medication side effect, substance
 withdrawal /intoxication, or multiple causes
Delirium - Diagnosis

DSM IV Eliminated
•   Reduced level of consciousness
•   Sleep disturbance
•   Disorganized thinking
•   Changing psychomotor activity
Delirium - Diagnosis
The diagnosis is missed 33-67%
 of the time by physicians directly
 involved by patient care

• Individual presentation
• Presentation of illness in older cohort
• Differential diagnosis
Delirium - Diagnosis
Individual Presentation
• Patient dozes off when you’re trying
  to talk to her, you wake her up and 2
  minutes later she goes off to sleep again
Delirium - Diagnosis
Individual Presentation
• Mr. P. keeps picking at the bedclothes while
  you’re trying to talk to him
• Patient can’t repeat 3 words after you
Delirium - Diagnosis
Individual Presentation
• 82 yr. old lady comes to clinic. Brought by
  her daughter. Patient has history of
  dementia and goes to Adult Day Center.
  Daughter brings her today because Mom
  wouldn’t eat, needed help to walk, sat in the
  chair all day at the Center and kept falling
  asleep for the whole day.
Delirium - Diagnosis
Individual Presentation
• Mini-Mental State Examination
• Digit Span Test
• Days of the week backwards
Delirium - Diagnosis
Presentation Differences in Older Patients
• Delirium may be the only presentation of
  severe illness in older patients
• “Silent” myocardial infarction (up to 40%)
• 25% of older people have no fever
  associated with pneumonia, tuberculosis
  endocarditis or sepsis
• 13% older bacteremic patients are afebrile


Delirium - ? Risk factors
Advanced age                Infections
Electrolyte abnormalities   CP disorders
Hypoalbuminemia             CNS disease
Gastro/GU disorders         Polypharmacy
Sensory deprivation         Trauma (falls,
                            fractures, pain)
Delirium - ? Risk factors
CAM assessment
Delirium Model
 Interaction between
 Vulnerability factors (predisposing factors)
 Precipitating factors (insults)
Delirium - ? Risk factors
13 Vulnerability factors (predisposing factors)
sex, age, severe illness, MMSE <24, history of
  confusion, 2 measures of social support, vision
  impairment, depressive symptoms, hearing
  impairment, assistance with ADLs and IADLs
              Visual impairment
          Severe illness on admission
            Cognitive impairment
Delirium - ? Risk factors
Precipitating factors (insults)

         Use of physical restraints
      Malnutrition (albumin <3g/dL)
> 3 Medications added within 24 hour period
         Use of a bladder catheter
             Iatrogenic events
Delirium - Intervention
Clinical trial-3 units (intervention/control)
852 pts -70 yrs. and older, no evidence of
  delirium on admission
              visual impairment
              severe illness
              cognitive impairment
              BUN/Cr >18
• Intermediate risk      1 or 2 factors present
• High risk              3 or 4 factors present
Delirium - Intervention
Intervention group
• Cognition-orientation, activities
• Sleep protocol
• Immobility-early mobilization protocol
• Visual impairment-visual aides, adaptors
• Hearing impairment-protocol
• Dehydration-recognition, repletion
Delirium - Intervention
100% follow-up
• Exposing 19 at-risk pts. prevented
  one from developing delirium; 15% to 9.9%
• No. of days of delirium (105 vs 161)
  and no. of episodes (62 vs 90)
  were lower in the intervention group
Delirium - Intervention
100% follow-up, Outcomes
• It was most effective in patients with
  intermediate risk at baseline (one to two
  risk factors) rather than the high risk group
  (3 or 4 risk factors)
• No difference in severity or recurrence rates
• Cost:$327 per pt. in the intervention group
Delirium - Treatment
3 Simultaneous Approaches
• Identification and treatment of the etiology
  of delirium
• Environmental modification
• Control of symptoms
Delirium - Etiology
• Extensive, multifactorial
• 87% of delirium had a clear etiology
• 56% patients had one etiology 44% had 2.8
• 62% of hip fracture patients had multifactorial
• 3 commonest etiologies are infection, metabolic
  disturbance and medications
Delirium - Etiologies
D   drugs
E   endocrine/endogenous depression
M   metabolic
E   ears/eyes
N   nutrition
T   tumor, trauma, toxins
I   infections
A   atherosclerotic CD, alcohol
Delirium - Treatment
Step 1
• Suspect it
• Baseline cognitive status on admission
• Nursing staff
Delirium - Diagnosis
Step 2
• History and Physical
• Medication review
• Labs: CBC, lytes, BUN/Creatinine, glucose,
  calcium, phosphate, liver enzymes, ABG;
  blood alcohol & ammonia level if indicated
• Look for occult infection
Delirium - Diagnosis
Step 3 -No diagnosis
• More labs: Mg, TSH, drug levels, tox. screen
• CSF examination
• MRI with diffusion weighted imaging if new focal
  neurological finding, or suspected new CVA
• EEG especially useful to exclude non-controlled
  seizure activity-Diffuse slowing in both delirium
  (marked) and dementia. (EEG findings in alcohol
  or sedative-hypnotic withdrawal is fast)
Delirium - Diagnosis
Step 3 -No identifiable etiology
• Vigilance
• Daily physical examinations
• Daily laboratory tests
Delirium - Treatment
    Environmental modification
•   Improve orientation, clocks, calendars
•   Windows, appropriate lighting
•   Hearing aids and glasses
•   Family members involved
•   Mobility, no restraints, remove catheters
•   Patient placed at nurses station
Delirium - Treatment
Symptom control
Should never replace diagnostic workup and
  management of underlying illness
Only use if behavior interferes with
  diagnostic workup or prevents delivery
  of necessary medical care
Delirium - Treatment
Pharmacologic treatment
No blinded randomized controlled trials
Haldol 5mg po/im for episode of delirium
          True/ False
Delirium - Treatment
Pharmacology Dopamine
• Inc. cerebral dopamine levels can cause
• Dopamine inhibition can eliminate
  symptoms of delirium
• Made in 4 major CNS pathways
Antagonize dopamine by
 Decreasing synthesis
 Decreasing release
 Blocking dopamine receptors
Delirium - Treatment
Pharmacology Dopamine
Decrease synthesis
Alpha-methyl para-tyrosine inhibits dopamine
  formation by blocking tyrosine hydroxylase
  but this enzyme is also used to synthesize
  norepinephrine which results in widespread
  autonomic nervous system effects
Delirium - Treatment
Pharmacology Dopamine
Decrease release
Reserpine and tetrabenzine are very potent
  dopamine antagonists but they also inhibit
  vesicular storage of norepinephrine and
Delirium - Treatment
Pharmacology Dopamine receptor blockade
4 dopaminergic pathways: nigrostriatal,
  mesolimbic, mesocortical, hypothalamus
  Phenothiazines and haloperidol are
  dopaminergic specific
5 dopamine receptors D1, D2, D3, D4, D5,
• Assoc. with adenyl cyclase D1 group D1,5
      Independ. of adenyl cyclase D2 group
• Antipsychotics block the D2 group
Delirium - Treatment
Symptom treatment Haldol

• Haloperidol sedates, treats hallucinations,
  paranoia and delusions, less anticholinergic and
  less hypotensive than other antipsychotics
• Rapid onset, relatively wide therapeutic window,
  reasonable safety profile, no active metabolites,
  antipsychotic effects can last 3-6 days, various
  administration routes
Delirium - Treatment Haldol
• 2mg/day of haloperidol results in 53% to 74% of
  D2 receptor occupancy. Thresholds of 60%
  occupancy exert antipsychotic activity. A higher
  occupancy rate of 80% may increase side effects
  with no appreciable improvement clinically.
• Schizophrenia: daily doses of 10mg/day
• Extrapyr. effects, akathisia, tardive dyskinesia
• Neuroleptic malignant syndrome: fever, delirium,
  tremulous rigidity, & autonomic hyperactivity
Delirium - Treatment
Pharmacologic treatment Haldol
• Starting dose 0.5mg
• Maximum dose 3-5mg/24 hours
• Repeat every 30 minutes until desired effect
• Taper the dose given in the first 24 hours
  over 3-5 days (largest amount before bed)
• Abrupt withdrawal can ppt. recurrence
Delirium - Treatment
Pharmacologic treatment
• Benzodiazepines if sedation is key
• Benzodiazepines potentiate
  the action of antipsychotics
• Lorazepam 0.25mg to 0.5mg can be used
• Can make delirium worse, can precipitate
  paradoxical agitation: Discontinue it
Delirium - Terminal Delirium
• More than two thirds of Americans die in acute
  care settings
• Term confined to delirium within last one to two
  days of life
• Prevalence rates as high as 85%
• Recognizing delirium in this cohort prevents
  common delirious symptoms such as agitation
  from being interpreted as pain
• Multiple etiologies most likely
• Hallucinations may be present; treat promptly
1. Delirium instead of Altered Mental Status
2. It is common and important
3. Target patients and suspect it early
4. Inattention, Digit Span Test, Days of the
  week backwards
5. Treat the underlying etiology, check meds
6. Haldol; Start LOW, GO SLOW
7. May take days, weeks, months to clear

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