Delirium by Klause

1. DELIRIUM
Klause Niyonsenga
Bms/2439/153/Du

2. CASE 1
An 81 year old man with diagnosis of benign prostate
hypertrophy and hypertension. He was doing fine until 3 days
prior to admission when he came in with history of low-grade
fever and nocturia and poor sleep. Daughter gave him
diphenhydramine for sleep. On the day of admission, he
became confused, had high grade fever, no loss of
consciousness or vomiting. In his social history, he smokes
tobacco occasion ally.
At the hospital, he was diagnosed with a UTI. 6 hours after
admission, he became combative, agitated and confused. He
pulled out the IV line and insisted on going home.

3. OUTLINE
 Definition
 Clinical Signs and
Symptoms
 Causes / Risk factors
 Pathophysiology
 Epidemiology
 Classification
 Differentials
 Management
 Complications
 Prognosis
 Conclusion

4. Definition
Delirium is a transient, acute global disorder of cognition. It is
defined as a transient, usually reversible, cause of mental
dysfunction and manifests clinically with a wide range of
neuropsychiatric abnormalities.
It can occur at any age, but it occurs more commonly in patients
who are elderly and have multiple medical problems or a previously
compromised mental status. A study showed 50% of elderly
patients in the hospital will have an episode of delirium at some
point.
It is a medical emergency associated with increased morbidity and
mortality rates. It is often unrecognized or misdiagnosed.

5. Clinical Characteristics
 Develops acutely (hours to days)
 Characterized by fluctuating level of consciousness
 Wandering attention
 Distractible by irrelevant stimuli
 Agitation or hyper somnolence
 Extreme emotional liability
 Affective symptoms (anxiety, fear, depression, irritability, anger,
euphoria, apathy)
 Shifts on psychomotor activity (picking at clothes, attempts to get out
of bed when unsafe, sudden movements, sluggishness, lethargy.
 Cognitive deficits can occur

6. Cognitive deficits
 Language difficulties: word finding difficulties, dysgraphia
 Speech disturbances: slurred, mumbling, incoherent or disorganized
 Memory dysfunction: marked short-term memory impairment, disorientation
to place, time and rarely person.
 Perceptions: misinterpretations, illusions, delusions and/or visual (more
common) or auditory hallucinations
 Constructional ability: can’t copy a pentagon

7. Signs and Symptoms
 Distractibility, (impaired concentration)
 Disorientation in time, place, rarely person
 Misinterpretations
 Illusions
 Hallucinations
 Speech/language disturbances (dysarthria, dysnomia, dysgraphia, dysphasia)
 Affective/mood symptoms (anxiety, fear, depression, irritability, anger, euphoria,
apathy)
 Tremors
 Shifts in psychomotor activity ( sudden movements, sluggishness,agitation which
can lead to falling or pulling out IV lines or catethers,9 lethargy, combatibe
behavior)

8. Based on the psychomotor activity, delirium can be described
as hyperactive, hypoactive or mixed.
Hyperactive delirium –the patient is hyperactive, combative and uncooperative, May
appear to be responding to internal stimuli, Frequently these patients come to our attention because
they are difficult to care for.
[ agitation, restlessness, hallucinations or delusions. Common in alcohol withdrawal
or drug intoxication]
Hypoactive delirium – Pt appears to be napping on and off throughout the day, Unable to
sustain attention when awakened, quickly falling back asleep, Misses meals, medications, appointments, Does
not ask for care or attention, This type is easy to miss because caring for these patients is not problematic to
staff
[lethargy, drowsiness, apathy, decreased responsiveness, slowed motor skills.
Common in hepatic encephalopathy , hypercapnia and in elderly]
Signs and Symptoms cont’d

9. …
Mixed delirium – a combination of both types just described
[either relatively normal levels of psychomotor activity or
rapidly fluctuating levels of activity]
The most common types are hypoactive and mixed
accounting for approximately 80% of delirium
cases

10. Risk factors
• Previous delirium
• Nursing home residents (incidence 60%)
• Polypharmacy (e.g. anticholinergic)
• Hospitalization (incidence 10-56%)
• Old age (especially males >80)
• Severe illness (e.g. cancer, AIDS)
• Recent anesthesia or surgery
• Substance abuse
• Pre-existing cognitive impairment, brain pathology,psychiatric
illness

11. Eitology (Drugs)
 Anticholinergics (furosemide,
digoxin, theophylline,
cimetidine, prednisolone,
TCA’s, captopril)
 Analgesics (morphine,
codeine..)
 Steroids
 Antiparkinson (anticholinergic
and dopaminergic)
 Sedatives (benzodiazepines,
barbiturates)
 Anticonvulsants
 Antihistamines
 Antiarrhythmics (digitalis)
 Antihypertensives
 Antidepressants
 Antimicrobials (penicillin,
cephalosporins, quinolones)
 Sympathomimetics

12. Predisposing Factors
 >60 years of age
 Childhood ( febrile illness,
anticholinergic use)
 Male sex
 Visual impairment
 Underlying brain pathology
such as stroke, tumor,
vasculitis, trauma, dementia
 Major medical illness
 Recent major surgery
 Recent anesthesia
 Depression
 Functional dependence
 Dehydration
 Substance
abuse/dependence
 Hip fractures
 Metabolic abnormalities
 Polypharmacy

13. Precipitating Factors
 Medications (see list)
 Severe acute illness
 UTI
 Hyponatremia
 Hypoxemia
 Shock
 Anemia
 Pain
Orthopedic surgery
Cardiac surgery
ICU admission
High number of hospital
procedures

14. CAUSES: ‘I WATCH DEATH’
• Infectious (encephalitis, meningitis, UTI, pneumonia)
• Withdrawal (alcohol, barbiturates, benzodiazepines)
• Acute metabolic disorder (electrolyte imbalance, hepatic or renal failure)
• Trauma (head injury, post-operative)
• CNS pathology (stroke, hemorrhage, tumour, seizure disorder, Parkinson’s)
• Hypoxia (anemia, cardiac failure, pulmonary embolus)
• Deficiencies (vitamin B12, folic acid, thiamine)
• Endocrinopathies (thyroid, glucose, parathyroid, adrenal)
• Acute vascular (shock, vasculitis, hypertensive encephalopathy)
• Toxins: substance use, sedatives, opioids (especially morphine), anesthetics,
anticholinergics, anticonvulsants, dopaminergic agents, steroids, insulin, glyburide,
antibiotics (especially quinolones), NSAIDs
• Heavy metals (arsenic, lead, mercury)

15. Important Rule-outs
 Wernicke’s
 Hypoxia
 Hypoglycemia
 Hypertensive
encephalopathy
 Meningitis/encephalitis
 Poisoning
 Anticholinergic
psychosis
 Subdural hematoma
 Septicemia
 Subacute bacterial
endocarditis
 Hepatic or renal failure
 Thyrotoxicosis/myx-
edema
 Delirium tremens
 Complex partial seizures

16. Pathophysiology
 Not fully understood
 Main theory = reversible impairment of cerebral oxidative
metabolism + neurotransmitter abnormalities
 Ach – anticholinergics = cause of acute confusional states + Pts
with impaired cholinergic transmission (eg Alzheimers) are more
susceptible
 Dopamine – excess dopamine in delirium
 Serotonin – increased in delirium
 Inflammatory mechanism – cytokines eg interleukin-1 release from
cells
 Stress reaction + sleep deprivation
 Disrupted BBB may cause delirium

17. Epidimiology
approximately 40% of hospitalized elderly pts >65 yr
approximately 50% of pts post-hip fracture
approximately 30% of pts in surgical intensive care
units
approximately 20% of pts on general medical wards
approximately 15% of pts on general surgical wards

18. Testing
 Mini mental status exam (MMSE) is not sensitive in
identifying delirium however repeated MMSEs can reveal
waxing and waning course
 Most sensitive items are serial 7’s, orientation, recall
memory
 Tests of attention include serial 7’s, spelling WORLD
backwards, months of the year backward, counting
down from 20

19. How do you evaluate a patient with
suspected delirium?
 Look at chart notes with particular attention to level of consciousness, behavior
and level of cooperativeness
 Look at the overall time course
 Review med list including scheduled, prns doses, recent meds discontinued or
started
 Evaluate for recent medical illness and interventions
 Screen for history of substance dependence to determine risk of withdrawal
 Review diagnostic studies including labs, imaging, vital signs
 Interview patient paying close attention to concentration, level of somnolence,
mood lability, executive function, short term memory deficits, kinetics. Use MMSE.
 Gather collateral information from family/friends regarding baseline function,
personality, psych history

20. Classification
Classification of Delirium
A. Dellrium due to a general medical condition(specify which
condition)
B. Delirium due to substance intoxication(specify which substance)
C. Dellrium due to a substance withdrawal (specify which substance)
D. Delirium due to a multiple etiologies(specify which conditions)
E. Delirium not otherwise specified(unknown etiology or due to other
causes such as sensory deprivation)

21. Diagnosis
Short Confusion Assessment Method
Confusion Assessment Method (CAM) for Diagnosis of
Delirium
Highly sensitive and specific method to diagnosis delirium
Part 1: an assessment instrument that screens for overall
cognitive impairment.
Part 2: includes four features found best able to distinguish
delirium from other cognitive impairments
Need (1) + (2) + (3) or (4)
(1) Acute onset and fluctuating course
(2) Inattention
(3) Disorganized thinking
(4) Altered level of consciousness -hyperactive or hypoactive

22. Diagnosis cont’d
Diagnostic Criteria – DSM 5
A. A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift atten
tion) and awareness (reduced orientation to the environment).
B. The disturbance develops over a short period of time (usually hours to a few days), rep
resents a change from baseline attention and awareness, and tends to fluctuate in se
verity during the course of a day.
C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language,
visuospatial ability, or perception).
D. The disturbances in Criteria A and C are not better explained by another preexisting,
established, or evolving neurocognitive disorder and do not occur in the context of a
severely reduced level of arousal, such as coma.
E. There is evidence from the history, physical examination, or laboratory findings that the
disturbance is a direct physiological consequence of another medical condition, sub
stance intoxication or withdrawal (i.e., due to a drug of abuse or to a medication), or
exposure to a toxin, or is due to multiple etiologies.

23. Specify whether
 Substance intoxication delirium: This diagnosis should be made instead of
substance intoxication when the symptoms in Criteria A and C predominate in the
clinical picture and when they are sufficiently severe to warrant clinical attention.
 Substance withdrawal delirium: This diagnosis should be made instead of
substance withdrawal when the symptoms in Criteria A and C predominate in the
clinical picture and when they are sufficiently severe to warrant clinical attention.
 Substance withdrawal delirium: This diagnosis should be made instead of
substance withdrawal when the symptoms in Criteria A and C predominate in the
clinical picture and when they are sufficiently severe to warrant clinical attention.
 Delirium due to another medical condition: There is evidence from the
history, physical examination, or laboratory findings that the disturbance is
attributable to the physiological consequences of another medical condition.
 Delirium due to multiple etiologies: There is evidence from the history,
physical examination, or laboratory findings that the delirium has more than one
etiology (e.g., more than one etiological medical condition; another medical condition
plus substance intoxication or medication side effect).

24. Specify if
 Acute: Lasting a few hours or days.
 Persistent: Lasting weeks or months.
 Hyperactive: The individual has a hyperactive level of psychomotor activity that may
be accompanied by mood lability, agitation, and/or refusal to cooperate with medical
care.
 Hypoactive: The individual has a hypoactive level of psychomotor activity that may
be accompanied by sluggishness and lethargy that approaches stupor.
 Mixed level of activity: The individual has a normal level of psychomotor activity
even though attention and awareness are disturbed. Also includes individuals whose
activity level rapidly fluctuates.
 Regarding course, in hospital settings, delirium usually lasts about 1 week, but some
symptoms often persist even after individuals are discharged from the hospital.
Individuals with delirium may rapidly switch between hyperactive and hypoactive
states. The hyperactive state may be more common or more frequently recognized
and often is associated with medication side effects and drug withdrawal. The
hypoactive state may be more frequent in older adults.

25. Investigations
• Standard: CBC and differential, electrolytes, Ca2+, PO43-,
Mg2+, glucose, ESR, LFTs, Cr, BUN, TSH, vitamin B12,
folate, albumin, urinalysis
• As indicated: ECG, CXR, CT head, toxicology/heavy metal
screen, HIV, blood cultures,
EEG (typically abnormal - generalized slowing or fast
activity, can also be used to rule out underlying seizures or
post-ictal states as etiology)
• Indications for CT head: focal neurological deficit, acute
change in status, anticoagulant use, acute incontinence,
gait abnormality, history of cancer.

26. Differential Diagnosis
To establish if the disorder is organic or functional
- Organic
- The cognitive disorder preceded the mood or other disorder
- Cognitive defects occur in specific areas of intellectual function
- The presence of symptoms seldom found in non – organic
disorder such as visual hallucinations
- Functional
- By exclusion of organic causes
- By finding positive evidence of psychological etiology

27. Differential diagnosis – cont’d
Features Delirium Dementia
Onset Acute Insidious
Course Fluctuating Progressive
Duration Days – weeks Months - years
Consciousness Altered Clear
Attention Impaired Normal (unless
severe)
Psychomotor
changes
Increased or
decreased
Often normal
Reversibility Usually Rarely
Thinking Disorganized Impoverished
Differentiating features of delirium and dementia

28. Differentiating Delirium from other
psychiatric disorders
 Clouded consciousness or decreased level of alertness
 Disorientation
 Acuity of onset and course- serial mental status exams
can help demonstrate this
 Age >40 without prior psych history
 Presence of risk factors for delirium, recent medical
illness or treatment

29. Delirium Vs Dimentia
 Dementia has an insidious onset, chronic memory and
executive function disturbance, tends not to fluctuate. In
delirium cognitive changes develop acutely and
fluctuate.
 Dementia has intact alertness and attention but
impoverished speech and thinking. In delirium speech
can be confused or disorganized. Alertness and
attention wax and wane.

30. Delirium Vs Schizophrenia
 Onset of schizophrenia is rarely after 50.
 Auditory hallucinations are much more common than
visual hallucinations
 Memory is grossly intact and disorientation is rare
 Speech is not dysarthric (slurred)
 No wide fluctuations over the course of a day

31. Delirium Vs Mood Disorders
 Mood disorders manifest persistent rather than labile
mood with more gradual onset
 In mania the patient can be very agitated however
cognitive performance is not usually as impaired
 Flight of ideas usually have some thread of coherence
unlike simple distractibility
 Disorientation is unusual in mania.

32. Management
 Identification and reversal of the cause is the definitive treatment.
 The search must be thorough, as in the diagnosis and treatment of any other
organ system failure.
 Delirium is brain failure!
1. Identify + treat underlying cause (return to pre-morbid state can take up to 3 weeks)
2. Rule out EtOH withdrawl
3. Ensure adequate oxygenation
4. Assume an underlying organic cause
5. Ensure adequate hydration + nutrition
6. Use clear, straightforward communication
7. Orientate the patient to environment + frequent reassurance
8. Identify if environmental factors are contributing to confused state

33. Management cont’d
 Disturbed, agitated or uncooperative patients often require additional nursing
input.
 Medication should not be regarded as first line treatment.
 Consider medication if all other strategies fail but remember all psychotropic
meds can increase delirium + confusion.
Behavioral/Environmental Strategies
 Reorientation, calendars, clocks
 Room near nursing station
 Lights on/off during day/night
 Windows
 Family/familiarity
 Hearing aids, glasses
 Avoid restraints

34. Pharmacological management.
 Pharmacological Therapy
 Nothing FDA-approved
 Antipsychotics are treatment of choice for agitation compromising care or safety
 Haloperidol best studied, widely used
 Virtually no anticholinergic effects
 Virtually no hypotensive effects
 Risk of EPS (akathisia), rare with IV route
 EPS rare when IV route used, however, IV route carries risk of QTc
prolongationrisk of TdP
 Risk greatest with higher doses over shorter periods of time, in pts with QTc
>450
 Monitor EKG and electrolytes (K, Mg)
 Monitor for akathisia
 Recent evidence suggests not to use in patients with dementia or risk of CVD due
to increased risk of cerebral ischaemia.

35. Benzodiazepines
Primarily indicated in EtOH or benzodiazepine withdrawal delirium
Adjunct to neuroleptics in treatment of severe agitation
Lorazepam 0.5-1mg tds orally
 Shorter half life than diazepam + effective at lower doses
 S/E -Respiratory depression, increased risk of falls, hypotension
 Not for long term use
 Generally avoided as may WORSEN delirium--especially hepatic
encephalopathy
 Variable
 Full recovery (unlikely at time of hospital d/c in the elderly, may take several
weeks)
 Persistent cognitive deficits (new “baseline”)
 Stupor, coma, death (the presence of delirium indicates a more serious medical
illness, affecting the central nervous system)

36. Management cont’d
Atypical Antipsychotics
Risperidone 0.25-0.5 po bid prn
ODT available
Olanzapine 2.5 mg qhs
IM/ODT available
Caution: sedating, anticholinergic
Quetiapine 25 mg po bid
Limited data on aripiprazole, ziprasidone (concern for QTc prolongation)
 Cochrane Review 2007
 Meta-analysis compared efficacy and adverse effects (3 trials included)
 No difference in efficacy or adverse effects between low dose haloperidol and
risperidone and olanzapine
 High dose haloperidol (>4.5 mg/d) greater incidence of SE, mainly EPS

37. Education
 Let the family know what is going on including that
delirium waxes and wanes and can last for several
weeks
 Once the patient starts to improve explain to them what
delirium is, how common it is and the usual course. It is
very frightening for them and may fear they have a
psychiatric illness.

38. Case 2
A 79 year old man with dementia, DMII, CAD, COPD, and acute renal failure but no
other psychiatric history was admitted for pneumonia. After a 3 week hospital
course complicated by delirium, hyponatremia, and UTI, he has been less
agitated, more cooperative and more oriented for 2 days in association with
decreased wbc and lessened oxygen requirements. You are consulted for acute
suicidal ideation.
What initial plan would be best?
a. Assign a sitter (1:1), evaluate patient for antidepressant, provide supportive
psychotherapy to address prolonged hospitalization
b. Assign a sitter (1:1), check urinalysis, do a chest x-ray, begin SSRI
c. Transfer to psychiatry for further care
d. Evaluate for a sitter (1:1), check urinalysis, do a chest x-ray, discuss with primary
team

39. Case 2 - Discussion
Answer = D: Evaluate for a sitter (1:1), check urinalysis, do a
chest x-ray, discuss with primary team
Delirium must be ruled out first in this case…it offers more
morbidity than depression in this setting and this patient is at
higher risk for having delirium. Suicidal ideation is common in
delirium. Adding an antidepressant may worsen the picture—
better to wait 2-3 days to rule out delirium, as that delay will not
greatly impact treatment of depression; but, misdiagnosing as
depression may result in failing to search for the cause of the
delirium.

40. Case 3
Consult requested for 85 yo female with h/o dementia recently admitted to the
SNF, following hospitalization for hip fracture/repair , complicated by post-op
infection. Pt noted by staff to be disoriented, “sundowning,” and resistant to
care and PT. Per staff, family concerned that her dementia is “much worse”
than before her surgery despite apparently successful surgery and resolution
of her infection.
What initial plan would be best?
A) Send her to the ER
B) Review chart including medication list, talk to staff/family, physical and
mental status exams
C) Begin routine haloperidol 0.5 mg TID for agitation
D) Begin lorazepam 1 mg with dinner for sundowning behaviors

41. Case 4
70 yo male with no reported psychiatric history admitted for elective
surgery. Doing well post-op until development of acute confusion,
agitation, paranoia, trying to pull out lines and demanding to leave
AMA. Exam reveals a diaphoretic, tremulous man with tachycardia and
elevated BP. Which are part of the initial treatment plan?
A) Begin olanzapine 5 mg q4h routine for agitation
B) Transfer directly to psychiatry
C) Ensure safety of patient/staff
D) Obtain collateral information and history from family, review
chart/meds, complete physical and mental status examinations
E) Initiate alcohol detox protocol with lorazepam
F) Check CMP, CBC, UA, urine tox, ammonia

42. Complications
 Malnutrition
 Aspiration pneumonia
 Pressure ulcers
 Weakness, decreased mobility, decreased function
 Falls,
Prognosis
Patients can recorver completely f the cause is identified quickly
and addressed
Up to 50% 1 yr mortality rate after episode of delirium (some
sites say they die within 6 months)

43. CASE 5
 Mr R is 83 yo gentleman with a long history of hypertension, diabetes with
peripheral neuropathy and hypertension, and occasional angina admitted
to medicine 4 days ago for failure to thrive. Two weeks prior to admission
he missed his weekly bridge game which he has not done in 12 years. The
day prior to admission, his friend found him asleep in front of the TV and
was difficult to rouse. He was minimally communicative, had been
incontinent of urine and hadn’’t eaten in several days. His friend denied
history of mental illness, substance abuse and noted he is usually social
and friendly. On admission he was calm, cooperative but withdrawn. He
was hyponatremic and had a UTI which have been treated but he remains
somnolent and withdrawn. Current meds: insulin, atenolol, lisinopril,
temazepam, azithromycin, aspirin.temazepam. On exam he is quiet,
answers questions with monosyllabic answers, has poor eye contact and
scores a 9/30 on MMSE with very poor effort.

44.  He is presenting as a classic example of hypoactive delirium
however: Urinary incontinence with altered mental status should prompt
concerns about normal pressure hydrocephalus. He could have had a stroke or
fall given his diabetes, hypertension and peripheral neuropathy--he needs a head
CT. The UTI and hyponatremia could cause delirium and even with appropriate
treatment mental status may take weeks and even months in the elderly--some
may never return to baseline.
OTHER POSSIBLE CONTIBUTING FACTORS
 Meds such as benzodiazapines
 Glycemic abnormalities- how are his blood sugars?
 Would need to rule out alcohol withdrawal or overdose-always do a urine tox
screen
 Is he depressed?
 Is he demented?
 The low MMSE reveals severe impairment which is common in delirium. His poor
effort could signal inattention or depression.

45. Case 6
 Mr E is a 71 yo gentleman with hx of asthma, BPH and HTN admitted
to medicine 3 days ago for bilateral lower extremity cellulitis. A the
time of admission he was cooperative and oriented but over the
past 24 hours has become occasionally confused, agitated,
uncooperative and somnolent. He appears to be talking to someone
in his room when no one is there.
His current meds include: lisinopril, naproxen, cimetadine,
albuterol/ipratroprium inhaler, levofloxacin, oxygen via nasal canula
prn
He has no known psych history, drinks 1-2 glasses of wine/night
The medicine service is concerned he is psychotic and requests help
managing his behavior.
 When you speak to him he is difficult to rouse and falls asleep
several times. He struggles to maintain focus on questions and is
unable to perform the mental status exam. He believes he is in
Oklahoma and that you are his cousin.

46. What points to Delirium
 Altered mental status developing over a short period of time
 Alternating agitation, confusion and somnolence
 Auditory hallucinations in a 70 yo with no previous psych history
 Several of his meds could cause delirium including cimetadine, inhalers, naproxen.
He is also need O2 which indicates hypoxia at times
 Multiple medical possibilities including:
 Meds including cimetadine, inhalers, naproxen.
 Hypoxia- he is needing O2 at times
 Cellulitis
 Stroke with his history of HTN
 UTI with history of BPH
 Metabolic abnormalities including electrolyte or glucose disturbances, liver or
renal dysfunction, thyroid dysfunction
 Alcohol withdrawal

47. Conclusion
 Delirium is common in the geriatric population
 Dementia is a risk factor for delirium – patients
frequently have both
 Recognizing delirium, and distinguishing the syndrome
from primary psychiatric conditions is critical
 Delirium can present in a variety of ways and can be a
result of a number of etiologies
 Awareness of the hypoactive subtype of delirium is
important – avoid confusing it with depression
 Antipsychotic medications are useful in the management
of symptoms of delirium; benzodiazepines are useful in
cases of alcohol or benzodiazepine withdrawal, only.

48. References
Textbook of psychiatry
Medscape
Toronto notes
www.slideshare.com
www.google.com
www.wikipedia.com