Delirium

1. Delirium in the Elderly
Kirsten M. Wilkins, MD
Assistant Professor of Psychiatry
Yale School of Medicine
VA CT Healthcare System

2. Case 1:
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

3. Case 1 - 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.

4. Delirium
 DSM-IV-TR Criteria
 Disturbance of consciousness with reduced
ability to focus, sustain, or shift attention.
 A change in cognition (memory deficit,
disorientation, language disturbance) or the
development of a perceptual disturbance
(i.e. auditory or visual hallucinations) that is
not better accounted for by a preexisting
dementia.

5. Delirium
 DSM-IV-TR Criteria, cont.
 The disturbance develops over a short time
(hours to days) and fluctuates during the
day.
 There is evidence that the disturbance is
caused by the direct physiological
consequences of a general medical
condition or substance.

6. Delirium
DELIRIUM IS ALSO KNOWN AS….
 acute confusional state
 acute mental status change
 altered mental status
 brain failure
 hepatic encephalopathy
 organic brain syndrome
 toxic or metabolic encephalopathy

7. Delirium: Epidemiology
 Prevalence depends on population
 Greater in med/surg population
 Community 0.4 - 2%
 General hospital admissions ~20%
 On admission 10 – 15% elders
 During hospitalization up to 40%
 At end of life up to 83%
Trzepacz and Meagher 2005
Saxena and Lawley 2009
Fong et al 2009

8. Delirium: Epidemiology
 Higher rates seen with…
 Post-op (ortho, cardiothoracic, vascular)
 ICU admission
 Poor functional recovery
 Increased hospital lengths of stay
 Increased likelihood of NH placement
 Up to 60% NH pts have delirium
Trzepacz and Meagher 2005
Mittal et al 2011

9. Delirium - Impact
 Increased morbidity
 Poorer recovery from medical illness
 Increased need for walking devices
 6x increased risk of decubitus ulcers or
aspiration pneumonia
 Increased risk of future cognitive decline
 10-33% mortality rate in hospital
 Increased risk of mortality even months
after d/c Fong et al 2009
Siddiqi et al 2006

11. Case 2:
 Consult requested for 85 yo female with h/o dementia recently
admitted to 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. Which of the following may explain her
symptoms?
 A) Opioid pain medications
 B) Ongoing symptoms of delirium
 C) New cognitive “baseline”
 D) Old age
 E) A, B, and C

12. Delirium Risk Factors
 Age
 Preexisting dementia
 Recent surgery
 Bone fractures
 Infections
 Hypoalbuminemia
 Preexisting CNS structural abnormalities

13. Delirium Risk Factors
 Abnormal sodium
 Severe illness
 AIDS, Cancer
 Polypharmacy
 Dehydration
 Visual/hearing impairment

14. Delirium Risk Factors
 Substance Abuse
 Alcohol
 Prescription drugs
 Illicit drugs
 You must ask!
 Collateral informant

15. Delirium: Presentation
Three types
 Hyperactive
 Better recognized
 More attention to treatment
 Associated with improved outcome
 Hypoactive
 Little recognized
 Depression is primary differential
 Associated with poor outcomes
 Mixed

16. Delirium: Presentation
 Cognitive Symptoms
 Inattention
 Memory impairment
 Disorientation
 Behavioral Symptoms
 Agitation or hypoactivity
 Resistance to care
 Sleep-wake disturbance
 Psychiatric Symptoms
 Paranoia, delusions
 Hallucinations (often visual), illusions
 Affective lability

17. Disrupted Sleep-wake Cycle
 Insomnia
 Napping
 Being awake at night, limited light and external
cues leads to disorientation and paranoia
which may cause agitation
 Caution with sedative medications due to
concerns of worsening delirium

18. Affective Lability
 Mood may fluctuate widely in a very
short period of time (minutes/hours)
 Anxiety/panic/fear/anger
 Apathy/sadness - commonly mistaken
for depression
 Euphoria (esp. if steroid-induced)

19. Delirium:
Differential Diagnosis
 Dementia with Behavioral Disturbance
 Psychotic Disorder (Schizophrenia)
 Mood Disorder (Depression, Mania)
 Catatonia
 Others

20. Delirium versus Dementia
DELIRIUM
impaired memory +++
impaired thinking +++
clouding of consciousness +++
major attention deficit +++
fluctuation of course/day +++
disorientation +++
vivid perceptual disturbance ++
incoherent speech ++
disrupt sleep/wake cycle ++
nocturnal exacerbation ++
lack of insight ++
acute or sub acute onset ++
impaired judgment +++
DEMENTIA
+++
+++
-
+
+
++
+
+
+
+
+
-
+++

21. Delirium
Generally divided into 4 major types:
 Delirium secondary to general medical
condition
 Delirium secondary to substance
intoxication
 Delirium secondary to substance withdrawal
 Delirium secondary to multiple etiologies

22. Delirium
“Rarely is delirium caused by a single
factor; rather, it is a multifactorial
syndrome, resulting from the interaction
of the vulnerability on the part of the
patient (ie, predisposing conditions—
cognitive impairment, severe illness,
visual impairment) and hospital-related
insults (ie, medications and
procedures).” –Inouye et al 2007

23. Source: Matrix Advocare Network wesite

24. Case 2:
 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

25. Etiologies of Delirium
 Urgent recognition
 Wernicke’s
 Hypoxia
 Hypoglycemia
 Hypertensive encephalopathy
 Intracerebral hemorrhage
 Meningitis/encephalitis
 Poisoning/medications

26. Etiologies -“ I WATCH DEATH “
 I = Infection
 W = Withdrawal
 A = Acute Metabolic
 T = Trauma
 C = CNS Pathology
 H = Hypoxia
 D = Deficiencies
(especially vitamin)
 E = Endocrinopathies
 A = Acute Vascular
 T = Toxins
 H = Heavy metals

28. Etiologies of Delirium
General Medical Conditions
 HIV/AIDS
 Orthopedic procedures (50%)
 Infectious (UTI, Pneumonia, Sepsis)
 Metabolic derangement
 Cancer (PLE, brain mets—L, B, M)
 Impaction, constipation, dehydration, many,
many others…

29. Etiologies of Delirium
 Iatrogenic and polypharmacy
 Anticholinergic medications
 Opioids
 Benzodiazepines
 Steroids
 Antihistamines
 Antibiotics
 Many, many others…

30. Delirium: Neurobiology
 Best established neurotransmitter
dysfunction: reduced cholinergic activity
 Increased dopamine may also play a role
 Low and excessive serotonin
 Low and excessive GABA
Trzepacz and Meagher 2005

31. Delirium: Neurobiology
 Direct injury to the neurons
 Metabolic
 Ischemic
 Alters synthesis/release of neurotransmitters
 Stress response
 Trauma, surgery, infection  release of
proinflammatory cytokines, elevated cortisol
 Direct neurotoxic effects
 Alters neurotransmitter levels
Mittal et al 2011

32. Diagnosis of Delirium
 Delirium is a clinical diagnosis
 History and physical examination
(attention to VS)
 Mental Status Exam
 Rating Scales-consider on admission
 Confusion Assessment Method
 Delirium Rating Scale
 MMSE/Clock

33. Diagnosis of Delirium
 Lab tests cannot diagnose delirium but may
support dx
 CBC, CMP, UA, urine tox, TSH, B12, ammonia
 CXR, EKG, LP if indicated
 Neuroimaging
 EEG
 Generalized slowing in delirium, nonspecific
 Triphasic waves in hepatic encephalopathy
 Low voltage fast activity in EtOH or BZD w/d

34. Delirium: Management
 Identification and reversal of 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!

35. Delirium: Management
 Monitor VS and I/O
 Ensure good oxygenation
 D/C nonessential medications
 Minimize opioids, benzos, etc
 Repeat PE, further lab, radiologic studies
if cause not yet identified

36. Delirium: Management
 Behavioral/Environmental Strategies
 Reorientation, calendars, clocks
 Room near nursing station
 Lights on/off during day/night
 Windows
 Family/familiarity
 Hearing aids, glasses
 Avoid restraints

37. Delirium: 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

38. Delirium: Management
 Pharmacological Therapy
 Haloperidol
 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

39. Delirium: Management
 Antipsychotic Dosing in Elderly
 Use clinical judgment depending on severity of symptoms for starting
dose:
 Haloperidol
 0.5mg mild
 1mg moderate
 2mg severe
 Assess response to initial dose and repeat as needed, monitoring for
effectiveness and adverse effects
 Day one: order prn
 Day two and beyond: assess total drug needed previous day and
schedule that amount over the next day. Reassess daily continuing
process until delirium resolves.
 Once symptoms have remitted, continue effective dose for 48 hours,
then slowly taper and discontinue over 1-5 days, depending on
severity and duration of delirium up to that point. Avoid abrupt
discontinuation after first day or two of mental clarity to avoid risk of
rebound symptoms

40. Delirium: Management
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 prn
 Limited data on aripiprazole, ziprasidone
(concern for QTc prolongation)

41. Delirium: Management
 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
Lonergan 2007

42. Delirium: Management
 Antipsychotics
 Black box warning
 Increased risk of death/CVAE’s in pts with
dementia
 Use judiciously, continue to reassess R/B
ratio, taper when appropriate

43. Case 3:
 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

44. Delirium: Management
 Pharmacological Therapy
 Benzodiazepines
 Primarily indicated in EtOH or benzodiazepine
withdrawal delirium
 Adjunct to neuroleptics in treatment of severe
agitation
 Lorazepam preferred given its reliable
absorption from po/IM/IV routes
 Generally avoided as may WORSEN delirium--
especially hepatic encephalopathy

45. Prognosis
 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)

47. Prevention
 30-40% cases preventable
 Risk factor intervention (Inouye 1999)
 Standardized protocols for 6 risk factors:
 Reduced incidence of delirium
 Decreased total # of days and # of episodes
 No difference in:
 Severity of delirium
 Recurrence of delirium
Fong 2009
Inouye et al1999

48. 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.

49. References
Trzepacz PT, Meagher DJ. Delirium. In: Levenson JL, ed. Textbook of Psychosomatic Medicine. Arlington, VA:
American Psychiatric Publishing, 2005:91-130.
Saxena S, Lawley D. Delirium in the Elderly: a clinical review. Postgrad Med J. 2009;85(1006):405-413.
Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev
Neurol. 2009;5(4):210-220.
Mittal V, Muralee S, Williamson D, et al. Delirium in the elderly: a comprehensive review. Am J Alzheimer’s Dis
Other Dement. 2011 Mar;26(2):97-109.
Siddiqui N, House AO, Holmes JD. Occurrence and outcome of delirium in medical in-patients: a systematic
literature review. Age Ageing. 2006;35(4):350-364.
Lonergan E, Britton AM, Luxenberg J. Antipsychotics for delirium. Cochrane Database of Systematic Reviews
2007, Issue 2. Art. No.: CD005594. DOI: 10.1002/14651858.CD005594.pub2
Inouye SK, Bogardus ST Jt, Charpentier PA, et al. A multicomponent intervention to prevent delirium in
hospitalized older patients. N Engl J Med. 1999;340(9):669-676.