A. Definitions

1. Confusion: incapacity of patient to think with usual speed and clarity
2. Delirium: acute, temporary confusional state; waxing and waning attention
3. Amnesia:loss of ability to form memories despite alert state of mind
4. Dementia: chronic deterioration of all intellectual / cognitive functions
5. Confabulation: fabrication of stories due to inability to form new memories
6. Hallucination: perception of non-existant sensation
7. Organic Brain Syndrome
   1. Cognitive impairment or psychiatric symptoms
   2. Caused by a known medical or neurological condition

B. Characteristics

1. Epidemiology
   1. Very high incidence in older, general medical patients (15-50%)
   2. In hospitalized older patients with delirium, six month mortality ~25%
   3. Most of the mortality occurs in first month and is due to underlying causes of delirium
   4. Often misdiagnosed as depression or dementia
2. Risk Factors
   1. Increased age (>65 years)
   2. Prior cognitive inpairment: dementia, history of delirium, depression, cognitive impairment
   3. Severe illness and/or major surgery, other causes of immobility
   4. Infection
   5. Underlying disease: low albumin, azotemia, hepatic dysfunction, metastatic cancer
   6. Intoxication
   7. Male sex
   8. Drugs: polypharmacy, psychoactive drugs, anticholinergics, sedatives, alcohol abuse
   9. Current or prior CNS disturbances: stroke, other neurologic disease, CNS infection
3. Subtypes of Delirium
   1. Confusional (Hypoactive) State: drowsiness with diffusely slow EEG (including anti- cholinergic agents, acute alcohol intoxication)
   2. Vigilant (Hyperactive) State: normal or fast EEG (such as alcohol withdrawal syndrome)
4. Clinical Features [1]
   1. Acute onset, abruply over hours or days
   2. Fluctuating coarse: symptoms come and go, characteristic lucid intervals
   3. Inattention: difficulty focusing, sustaining, shifting attention, following commands
   4. Disorganized thinking: disorganized or incoherent speech, rampling conversation
   5. Altered level of consciousness: clouding of consciousness, reduced sense of surroundings
   6. Cognitive defects: typical gloable, or multiple deficits in cognition, language impairment
   7. perceptual disturbances: illusions or halluncinations in ~30% of cases
   8. Psychomotor disturbances - variants as described above
   9. Altered sleep-wake cycle: daytime drowsiness, nightime insomnia
   10. Emotional disturbances common, particularly with labile emotions, including paranoia
5. Symptoms usually develop over 2-3 days but can be acute
   1. Increased difficulty concentrating; restless irritability
   2. Tremulousness, insomnia, poor apatite
   3. Convulsions may occur in some patients (electrolyte disturbances common)
6. Symptoms progress with altered state of consciousness
   1. Patient inattentive with decreased perception
   2. Distressed and Perplexed
   3. Concentration reduced - cannot do serial 7's or spell "world" backwards
   4. Usually still oriented
   5. Hallucinations may occur, often visual
   6. Tremor or restless movements may occur

C. Causes [3]

1. Both predisposing (chronic) and precipitating (acute) factors are involved
2. Brain Damage
   1. Trauma leading to inflammation
   2. Brain Surgery
   3. Hemorrhage
   4. Tumor - primary CNS, Chloroma, metastatic disease
   5. Late stage cancer without brain metastases often present in older patients
   6. Increased Intracranial Pressure
   7. Vasculitis
   8. Encephalitis / Meningitis (including syphilis)
3. Toxins / Drugs
   1. Benzodiazapines - both use and withdrawal from these)
   2. Alcohol withdrawal (Delirium Tremens)
   3. Anti-cholinergics: scopalamine, atropine, anti-histamines
   4. Sedating Agents (new drugs or withdrawal): opiates, barbiturates, antidepressants
   5. Glucocorticoids
   6. Anti-parkinsonian agents
   7. Catecholamines / Sympathomimetics - especially in elderly
   8. Hallucinogens
   9. Combinations of any of the above agents (may be exacerbated with neuroleptics)
4. Metabolic
   1. Hyponatremia
   2. Hypoglycemia
   3. Hypoxia
   4. Hypo / Hypercalcemia
   5. Hypomagnesemia
   6. Hypothyroidism and Hyperthyroidism
   7. Liver Failure
   8. Renal Insufficiency (especially acute)
   9. Wernicke Encephalopathy - thiamine deficiency
5. Systemic Illness
   1. Pneumonia
   2. Sepsis of any etiology
   3. Major surgery (including hip fracture [4])
6. Acute waxing and waning mental status suggests Arteritis
   1. Granulomatous disease - for example, Sarcoidosis
   2. Systemic Lupus Erythematosus (SLE)
   3. Polyarteritis Nodosa (PAN)
   4. Vasculitis of the CNS (with systemic involvement)
7. Delirium at the end of life [5]

D. Delirium Versus Dementia and Psychosis

* Drug related movement disorders can occur as well
E. Diagnosis and Treatment of Sudden Changes in Mental Status (Table 5, Ref [6])

1. Establish intravenous access
2. Provide supplemental oxygen
3. Acess vital signs, airway patency, respiratory function
4. Correct cardiovascular / circulatory abnormalities
5. Access serum glucose levels
6. Correct hypothermia or hyperthermia
7. Evaluate for neurologic deficit, trauma
8. Sedation for extreme agitation
   1. Lorazepam (Ativan®) or other benzodiazepine
   2. Neuroleptic such as haloperidol (see below)
9. If indicated, administer dextrose, thiamine, naloxone
10. If infection (meningitis, sepsis) possible, give empiric antibiotics
11. Perform computerized tomography (CT) scan of head
12. Full chemistry, hematology, coagulation panel, blood pH
13. Toxin screen - both urine and blood
14. Attempt to identify and correct any other underlying disorders
15. Acute therapy with high potency neuroleptics
    1. Haloperidol iv, im or orally is usually agent of choice
    2. Dose of haloperidol is 0.5-2mg initially depending on perons' age, size, situation
    3. Start low with elderly: 0.5-1mg po qhs

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References

1. Inouye SK. 2006. NEJM. 354(11):1157
2. Lawlor PG, Fainsinger RL, Bruera ED. 2000. JAMA. 284(19):2427
3. Riordan SM and Williams R. 1997. NEJM. 337(7):473
4. Morrison RS, Chassin MR, Siu AL. 1998. Ann Intern Med. 128(12):1010
5. Casarett DJ and Inouye SK. 2001. Ann Intern Med. 135(1):32
6. Tancredi DN and Shannon MW. 2003. NEJM. 349(13):1267 (Case Record)