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Case 25
75-year-old woman with altered mental status - Mrs.
Kohn
Author: Valerie J. Lang, M.D., University of Rochester School of Medicine
Learning Objectives
1. Recognize that altered mental status in an older inpatient is a medical
emergency and requires that the patient be evaluated immediately.
2. Differentiate between delirium, dementia, and depression.
3. Identify the risk factors for developing altered mental status, including:
Dementia
Advanced age
Substance abuse
Comorbid physical problems such as sleep deprivation, immobility,
dehydration, pain, and sensory impairment
ICU admission
4. Thoroughly review prescription medications, over-the-counter drugs, and
supplements, and inquire about substance abuse when evaluating delirium.
5. Recognize the symptoms and signs of the most common and most serious
causes of altered mental status, including metabolic causes, such as
hyponatremia.
6. Perform a thorough diagnostic evaluation of altered mental status.
7. Manage the most common causes of altered mental status.
8. Describe the pathophysiology, presenting signs and symptoms, laboratory
interpretation, and the management of hyponatremia, including the risk of
too rapid or too delayed therapy of hyponatremia.
9. Write appropriate fluid and replacement orders for patients with common
electrolyte and metabolic disturbances.
Summary of Clinical Scenario: Mrs. Kohn is a 75-year-old woman with a history
of hypertension and chronic diuretic use who three days ago had surgical repair of
a fractured hip she sustained at home after a fall. She has received opioids for
pain control, and for the past two days she has been confused, inattentive, and
lethargic. Her exam is notable for the presence of a foley catheter and the
absence of focal neurological findings.

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Opiate use
Recent hip surgery

Key Findings from

Recent fall

History

Intraurethral catheter
Chronic diuretic use

Key Findings from

Non-focal neurological exam

Physical Exam

Differential
Diagnosis

Key findings from

Testing

Final Diagnosis

1.
2.
3.
4.
5.

Electrolyte disturbance
tract infection
Adverse reaction to medication
Subdural hematoma
Uncontrolled pain

Hyponatremia
Low serum osmolality

Delirium due to thiazide-induced euvolemic

hypotonic hyponatremia

Case Highlights: While completing this case, the student becomes skilled at
using the CAM to differentiate delirium from dementia or depression, at identifying
risk factors for delirium in the elderly hospitalized patient, and at performing a
thorough exam and ordering appropriate studies to determine the underlying
cause of delirium. The student also learns how to replace fluid and correct
electrolyte abnormalities that can cause delirium and how to advise patients upon
discharge to decrease the risk of falls at home, which can occur as a result of
delirium.

Key Teaching Points

Knowledge
Delirium
Epidemiology
Affects 30% of hospitalized elderly patients who normally live in the
community.
Affects 65% of hospitalized elderly patients who are admitted from nursing
homes.

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The incidence of delirium in patients admitted to the ICU is even higher.

The incidence of delirium in the hospital depends on both:
Baseline vulnerabilities of the patient.
Precipitating factors that occur during the hospitalization.
Risk factors
Advanced age
Dementia
Dehydration
Sleep deprivation
Immobility
Polypharmacy
Acute medical illness
Uncontrolled pain
Sensory deprivation due to visual or hearing impairment
Use of restraints or urinary catheter
Malnutrition
Depression
Alcohol abuse
High blood urea nitrogen to creatinine ratio
Intensive Care Unit admission
Differential
Think of the 3 Ds when evaluating an older patient with confusion
1. Dementia is a chronic confusional state that develops slowly, over months to
years.
2. Delirium is an acute disturbance in consciousness and perception with an
underlying medical etiology.
3. Depression is primarily a mood disorder but can present as confusion in
older adults.
Diagnosis
U (CAM) The first two items and either the third or fourth item are criteria
for diagnosis of delirium: (A-I-D-A)
1. Acute onset and fluctuating course
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?
2. Inattention
Did the patient have difficulty focusing attention? For example,
are they easily distractible or do they have difficulty keeping
track of what is being said?
3. Disorganized thinking
Was the patient's thinking disorganized or incoherent, such as
rambling or irrelevant conversations, unclear or illogical flow of

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ideas, or unpredictable switching from subject to subject?

4. Altered level of consciousness
Overall, how would you rate this patient's level of
consciousness?
Alert = Normal
Vigilant = Hyper-alert
Lethargic = Drowsy, easily aroused
Stupor = Difficult to arouse
Coma = Unarousable
Orientation questions (to self, place and date) - Not part of the diagnostic
CAM because these items can be learned by a delirious patient if they are
asked frequently.
Inattention
Helpful in discriminating delirium from dementia.
Demented patients do not become inattentive until the dementia is
severe.
Examples:
Have the patient recite the days of the week or the months of
the year forward and backward. Especially useful with patients
who are illiterate or being interviewed through an interpreter.
Spell "world" backwards. (Requires English language and some
literacy.)
Serial 7's. (Counting back from 100 by subtracting 7's.) May be
falsely positive in a patient who is not educated or not good at
math.
Mini Mental State Exam - Not used to diagnose delirium. It is a screening
test for dementia.
Course
Although delirium usually resolves partially with treatment of the underlying
cause, more sensitive testing shows that it resolves completely in only 4%
of patients by the time of discharge. In 20% of cases it resolves completely
by three to six months.
Sequelae
Hypoactive: Increased risk of pressure ulcers, pulmonary emboli, and/or
aspiration pneumonia.
Hyperactive: Increased risk of falls with or without injury.
Inability to participate in care, eat properly, or take oral medications
properly.
Posttraumatic stress disorder may develop if memories of the confusion
occur.
Family members may also become anxious when they perceive that their
relative is acting crazy.
Increased length of stay and/or increased likelihood of requiring
institutionalization at discharge.

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Increased mortality. Patients who develop delirium in the hospital have a

2-fold increase in their 1-year mortality, independent of their underlying
medical problems.
Falls
Risks
Agitation
Visual impairment
Motor impairment
Need for frequent toileting
History of falls
Electrolyte imbalance
Hypokalemia
Hyponatremia -

Indirectly leads to

Serum sodium level

delirium if there is

Hyperkalemia -

<136 mmol/L

respiratory or cardiac

Indirectly leads to delirium

failure

in the case of cardiac

Disorientation

arrhythmias and/or failure.

Lethargy

Severe muscle

Weakness

weakness

Severe muscle

Muscle cramps

Cramps

weakness or

Headache

Tetany

paralysis

Nausea

Paresthesias,

Cardiac conduction

Vomiting

Muscle tenderness

abnormalities and

Restlessness

Constipation

cardiac standstill

Depressed

Ileus

reflexes

Tetany

Seizures

Hypo- or

Coma

hyperreflexia

Permanent brain
damage
Brain herniation
Respiratory
arrest and death
in serious cases

Steps to determine the underlying cause of hyponatremia

Step 1: Determine serum tonicity - Effective osmolality = Measured osmolality BUN/2.8
Differential

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Etiology

Underlying
cause

Effect

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Differential

Etiology

Artifact of
Psuedohyponatremia
assay

Underlying
cause

Effect

Indirect
Elevated lipids or measurement
proteins
of sodium is
falsely low

Hypertonic
hyponatremia

Presence
Mannitol or
of effective
glucose
osmols

Hypotonic
hyponatremia

-* Determine
volume status
for differential
-Impaired diagnosis. See
below
renal
-Primary
water
excretion polydipsia,
-Excessive irrigation of the
bladder or uterus
water
with sodium-free
intake
solutions during
hysteroscopy, or
transurethral
resection of the
prostate

Draws water
out of the
cells and into
the serum

Step 2: Assess volume status

Signs

Hypovolemic

Symptoms

Low JVP,
Vomiting, diarrhea,
orthostatic
diuretic use,
hypotension,
bleeding, & postural
& decreased
dizziness
skin turgor

Urine
Sodium

< 25
meq/L*

Examples: Diuresis (medication or osmotically

induced), adrenal insufficiency, salt-wasting
nephropathy, bicarbonaturia, ketonuria, diarrhea,
vomiting, blood loss, excess sweating, fluid
sequestration
> 40
meq/L

Euvolemic

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Examples: Syndrome of inappropriate antidiuresis

(SIAD), thiazide diuretics, hypothyroidism, adrenal

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Signs

Symptoms

Urine
Sodium

insufficiency, decreased solute intake (beer

potomania, tea and toast diet)
Shortness of breath,
orthopnea, &
paroxysmal
Hypervolemic nocturnal dyspnea

Anasarca,
pulmonary
edema/crackles,
& elevated JVP

> 40
meq/L

Examples: Congestive heart failure, cirrhosis, renal

failure, nephritic syndrome, & pregnancy
* Exceptions: Renal-salt wasting due to diuretics, cerebral salt wasting, and
Addisons disease urine sodium may be elevated, despite hypovolemia
Step 3: Assess urine osmolality: To determine the presence of antidiuretic
hormone (ADH). If ADH present, urine osmolality should be >150 mosm/kg,
reflecting ADH's effect of concentrating urine.
High urine osmolality:
High urine osmolality with low serum osmolality suggests the
inappropriate presence of ADH (because ADH should not be present if
serum osmolality is low).
Low urine osmolality (< 100 mosmol/kg) examples:
Primary polydipsia, because ADH secretion is shut down and the
kidneys respond by maximally diluting the urine.
Malnutrition states or beer potomania, where patients' solute intake
and stores are very low, causing decreased solute excretion.
Reset osmostat,"and the serum sodium level at which ADH release
occurs is lowered, causing stable mild-moderate hyponatremia.
Syndrome of inappropriate antidiuretic hormone (SIADH)
Most common causes
Disorders of the lung (small cell carcinoma, infections, positivepressure ventilation, acute respiratory failure)
Disorders of the central nervous system (mass lesions, trauma,
Inflammatory or demyelinating disorders, stroke, hemorrhage, acute
psychosis)
Less common causes
Drugs
Desmopressin
Oxytocin
Prostaglandin synthesis inhibitors
Nicotine
Phenothiazine
Tricyclics
Serotonin reuptake inhibitors

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Opiate derivatives
Chlorpropamide
Clofibrate
Carbamazepine
Cyclophosphamide
Vincristine
Uncontrolled pain
Tumors in other locations (mediastinal or extrathoracic)
Severe nausea
HIV infection
Surgery, very rare except those surgeries that involve the central
nervous system, lungs, or head/neck area

Skills
History
Time course Best obtained from nursing staff and family members who often
spend more time at the bedside than do physicians.
Physical Exam
Postural vital signs:
Obtain after being supine (lying down) for two minutes and after standing for one
minute.
Indicators of hypovolemia or inability to compensate for postural changes (e.g.,
due to autonomic insufficiency):
Fall in systolic blood pressure > 20 mm Hg with standing
Increase in pulse of > 30 beats/minute
Inability to stand long enough for vital signs because of dizziness
Signs of delirium:
Hypoactive delirium tends to be overlooked as opposed to hyperactive
Pulling at the bed sheets or pulling off clothes is common behavior
Studies
Complete blood count (CBC) - Reveals inflammation or anemia. Note older
patients with an infection may often have normal white blood cell counts.
A chemistry panel with electrolytes, glucose, and blood urea
nitrogen(BUN)/creatinine - Reveals hyper- and hyponatremia, hyper or
hypokalemia, or hypocalcaemia, renal failure, and hyper- or hypoglycemia.
Urinalysis Urinary tract infections are complications of urinary catheters
and immobility. Hematuria can be present as a result of trauma from the
urinary catheter. The catheter should be removed, and the urinalysis should
be rechecked after the hospitalization. If the hematuria persists, then

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further workup is needed.

Additional workup guided by findings on the history and exam:
Hepatic function panel Indicated when history of liver disease, alcohol
abuse, or hepatotoxic medications.
Urine toxicology screen Indicated if substance abuse is suspected.
Arterial Blood Gas (ABG) Indicated when history of respiratory
compromise or risk factors for an acid-base disorder.
Electroencephalography (EEG) Order if there is a history of seizure or
possible post-ictal state.
Cranial CT scan or cranial MRI scan Not routine, but order if intracranial
bleed or tumor is suspected.
Electrocardiogram (EKG)
Hypokalemia
Flattened T waves
U waves
ST segment depression
Prolonged QT interval

Hyperkalemia
Tall, peaked T waves
PR and QRS prolongation
Conduction blocks
Loss of p waves

Differential Diagnosis
1. Electrolyte disturbance
Common in hospitalized patients.
Fluctuations in sodium, potassium, calcium, and acid-base
disturbances can directly or indirectly lead to delirium.
Fluid shifts (dehydration or fluid overload) are common with surgery,
exacerbated by administration of excessive or inadequate intravenous
fluids and poor oral intake perioperatively.
Loop diuretics (e.g. furosemide) and thiazide diuretics (e.g. HCTZ) can
cause both hyponatremia and hypokalemia. They can also cause
dehydration.
2. Urinary tract infection (UTI) and other infections
UTI - very common, especially in elderly women.
In elderly patients, usually presents with confusion without classic
presenting signs and symptoms of dysuria, leukocytosis, or fever.
Foley catheters introduce bacteria to the bladder, which can lead to
infection.
Other infections, such as pneumonia, encephalitis, meningitis, may
also cause delirium, but are either less common or present with
localizing symptoms.
3. Adverse reaction to medication When a cause of delirium is identified, it is
usually a medication. There are many medications which may be well
tolerated by younger patients, but cause delirium in older patients,
especially when they are sick or have underlying cognitive impairment
Centrally acting benzodiazepines, opioids, anticholinergics, alpha-2
agonists

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Metabolically acting diuretics

Other antibiotics fluoroquinolones
*Acetaminophen does NOT cause delirium
4. Subdural hematoma Falls, especially in the elderly where there has been
some brain atrophy, can lead to subdural hematoma development without
the severe symptoms that would occur in a younger brain, and present as
delirium.
5. Uncontrolled pain Post-operative pain is often under-treated and can lead
to delirium.
Less likely diagnoses
Alcohol withdrawal syndrome Patients often under-report their baseline alcohol use, and alcohol
withdrawal may unexpectedly develop during hospitalization when
alcohol is not accessible.
Hyperadrenergic state with tachycardia, hypertension, diaphoresis,
and tremors as well as nausea and headache.
Alcoholic hallucinosis - hallucinations, usually visual or tactile, within
48 hours after the last drink.
Delirium tremens severe confusion and disorientation, usually begins
48-72 hours after the last drink.
Organ system failure Cardiac: Heart failure, as evidenced by orthopnea and/or paroxysmal
nocturnal dyspnea, elevated jugular venous pressure, crackles on lung
exam, and/or peripheral edema. Other cardiac issues, such as
arrhythmias, can cause delirium.
Pulmonary: COPD exacerbations can cause hypoxia or CO2 retention
and delirium.
Renal: Kidney failure may result in azotemia and delirium.
Hepatic: Liver failure may result in hyperammonemia and delirium.
Thyroid abnormalities:
Hypothyroidism- More common cause of delirium
Hyperthyroidism - Tachycardia and hypertension

Management
Delirium
Initial measures
Reorientation: Write date on message board and provide a large clock.
Avoid sensory deprivation: Use hearing aids and glasses when appropriate.
Aim for normalized sleep-wake cycle: Provide increased light and stimulation
during the day and provide low light and minimize interruptions at night.
Minimize restraints:
Use only as a last resort if patient is agitated and a harm to herself or
others.
Urinary catheters, intravenous lines, and nasal cannulas act like

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one-point restraints and should be used judiciously.

Prescribe adequate pain control:
Non-pharmacologic measures Prescribe hot/cold packs, limb
elevation, massage.
Non-opioids Prescribe around the clock or scheduled
acetaminophen or non-steroidal anti-inflammatory drugs.
Opioids Reserved for when pain is not controlled and prescribed in
lowest effective dose.
Pharmacologic measures
Sedative-hypnotics, such as benzodiazepines or diphenhydramine can
increase delirium in older patients.
Benzodiazepines are first-line for treating delirium caused by alcohol
withdrawal.
If a sleep agent is needed, trazodone is a safer alternative or a shorteracting benzodiazepine can be used if necessary.
A low dose of a neuroleptic, such as haloperidol 0.5 mg, is often helpful for
agitation if other measures are ineffective.
Falls
Preventive measures in the hospital
Treat underlying cause of delirium and/or agitation.
Remove unnecessary equipment or restraints.
Keep assistive devices (walker or cane) accessible.
Increase the number of nurses for high-risk patients.
Use a bedside commode and/or scheduled toileting for patients who require
frequent toileting.
Consider consulting a physical therapist.
Preventive measures upon discharge to home
Recommend group or individualized exercise programs to improve gait and
balance such as tai chi.
Prescribe gradual withdrawal of psychotropic medications, if any.
Refer for cataract surgery, when appropriate.
Recommend home safety interventions in adults with severe visual
impairment.
Recommend anti-slip shoe device for icy conditions.
Prescribe vitamin D supplementation for adults with vitamin D deficiency.
Fluid/electrolyte management
Correction of Hyponatremia
Volume status, duration, and severity of symptoms can guide correction of
hyponatremia.

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Use 0.9% saline for hypovolemia or with moderate symptoms to shut down
the bodys natural release of ADH in response to hypovolemia and raise
serum sodium 0.5 mmol/L per hour.
Use 3% saline for hypervolemia/euvolemia or with severe symptoms (coma
and/or seizures) and acute hyponatremia to raise serum sodium no more
than 1-2 mmol/L per hour or 8-10 mmol/L in the first 24 hours using the
least amount of fluid.
ADH receptor agonists (conivaptan, tolyvaptan) can be used to aid in
diuresis of solute-free water in severe cases of hypervolemic hyponatremia,
such as with congestive heart failure.
To estimate how much the serum sodium will rise with 1 liter of fluid, the following
formula can be used:
Change in serum sodium = ((Infusate Sodium + Infusate Potassium) Serum Na)/(Total Body Water + 1)
Total Body Water = Weight (in kg) x Percentage of Body Weight that is Water (The
fraction of body weight that is accounted for by total body water is affected by age
and gender; younger patients and men have a higher total body water content.)
Percentage of body weight that is total body water in various groups:
Non-elderly men: 0.6
Non-elderly women: 0.5
Elderly men: 0.5
Elderly women: 0.45
The infusate sodium contents of intravenous fluids are:
3% normal saline
0.9% saline
0.45% saline
Dextrose in water

513 mmol/L
154 mmol/L
77 mmol/L
0

If SIADH is the cause of the hyponatremia, giving the patient normal saline may
actually decrease the serum sodium. This is because the inappropriate excess of
antidiuretic hormone signals the kidney to hold onto free water. Infusing normal
saline will cause the patient to hold onto the water out of proportion to the
sodium. Thus, if SIAD is a consideration, it is key to also restrict the amount of
free water taken by mouth to one liter per day.
Complications of inappropriate electrolyte and fluid management

Osmotic demyelination (either central pontine myelinolysis or

extrapontine myelinosis) - Occurs when the hyponatremia is corrected too
rapidly and neuropsychiatric symptoms may not present until several days
after the correction of hyponatremia.
These symptoms include:

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Confusion
Quadriplegia
Pseudobulbar palsy
Catatonia
Locked-in syndrome
Parkinsonism
Mutism
Dystonia
Seizures - Caused by severe hyponatremia are indication for rapid
initial correction of the serum sodium.
Wernicke-Korsakoff syndrome Results when IV glucose solutions are
delivered without first correcting any thiamine deficiency because
thiamine is needed for glucose metabolism. Thiamine deficiency is
often present in alcoholic or malnourished patients.
Korsakoff psychosis - Confabulation (the filling in of gaps in
memory by unrestrained fabrication,) amnesia, and confusion.
Wernickes syndrome - Nystagmus, ophthalmoplegia, anisocoria,
ataxia, sluggish papillary reflexes, and potentially coma and
death.
Deep vein thrombosis prophylaxis
For prevention of DVT after hip surgery, prescribe a low molecular weight
heparin (e.g. enoxaparin or dalteparin), fondaparinux, or coumadin,
adjusted to a target INR of 2.5 (range 2-3).
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