1. Delirium
Hye Min Kim

2. Definition
AAFP: “Delirium is an acute, fluctuating syndrome of altered attention, awareness, and cognition precipitated by an underlying condition or event in vulnerable persons” (Kalish, Gillham, & Unwin, 2014).
Delirium usually develops suddenly, within hours or days; and its characteristic of confusional state is not explained by a preexisting or emerging dementia, but rather by other conditions or substances.

3. Diagnostic Criteria (DSM-V)
1) A disturbance in attention (reduced ability to direct, focus, sustain, and shift attention) and awareness.
2) The disturbance develops over a short period of time (usually hours to days), represents a change from baseline, and tends to fluctuate during the course of the day.
3) An additional disturbance in cognition (memory deficit, disorientation, language, visuospatial ability, or perception).
4) The disturbances are not better explained by another preexisting, evolving, or established neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma.
5) There is evidence from the history, physical examination, or laboratory findings that the disturbance is cause by a medical condition, substance intoxication or withdrawal, or medication side effect.
In sum, these features are describing a patient who suddenly developed unexpected, noticeable, and problematic changes in his or her attention and cognition with the objective findings that suggest the presence of other primary etiologies. Thus, delirium is rather a symptom arose from other medical conditions than a disease
(Francis & Young, 2014)

4. Pathogenesis Exact mechanism in unknown
Multiple, combined factors involved in delirium.
Neurotransmitters
Acetylcholine
Serotonin
Dopamine
Gamma-aminobutyric acid
Inflammatory
C-reactive protein (CRP)
Pro-inflammatory cytokines: Interleukins, Tumor necrosis factor-alpha (TNF-a)
Cortisol
Oxidative impairment
Strong relationship with occipital and subcortical regions?
Studies- hard to conduct with confused, acutely ill individuals.

5. Pathogenesis If level decreases  delirium symptoms Acetylcholine
Involved in attention, memory, organized thinking, and perception. (Decreases with aging)
Serotonin
Gamma-aminobutyric acid (GABA)
Level drops with withdrawal from hypnotic or sedative medications.
Oxygen
Cardiac disease, lung disease, anemia
Whenever mean arterial pressure drops
Anesthesia & adjuvant meds in pre-op  post-op delirium

6. Pathogenesis If level increases  delirium symptoms Aging
Dopamine: Hyperactive type with hallucinations and delusions
CRP, Proinflammatory cytokines: disruption in BBB function.
UTI, Pneumonia
Glucocorticoids: neuron cell damage/death by hypoxia, seizures, hypoglycemia, mitochondrial dysfunction…
Stress, major surgery hip fracture surgery
Aging
Decrease in cortical and white matter microvascular density
Decrease in mitochondria per endothelial cell
Decrease in capillary lumen size with greater tortuosity

7. Precipitating factors
Risk Factors
Predisposing factors
Precipitating factors
Aging
Male
Dementia
Immobility
Medical comorbidity
Hx of alcohol abuse
Sensory impairment
Acute MI
Acute Pulmonary events
Bed rest
Dehydration– fluid/electrolyte imbalances
Drug withdrawal
Medications – especially with psychoactive, anticholinergics, and opioid (30%)
Infection
Stroke – intracranial events
Uncontrolled Pain

8. Clinical Manifestations
DSM-V explains
Reduced ability to direct, focus, sustain, and shift attention
Reduced orientation to the environment
Distractibility- Disorganized flow of thoughts noticeable during conversation
Memory deficit, disorientation, disturbance in language (ex. loss of ability to speak in a secondary language) and visuospatial ability
Perceptual disturbance- Misidentify objects or persons
Visual or auditory hallucination
Fluctuation in severity- Worst in the evening and at night
Reversed sleep-wake cycle, anxiety, emotional lability, hypersensitivity to lights and sounds.

9. 3 Types Hypoactive: at least 4 (Depressive) Older adults Mixed Type
- Most common
Hyperactive: at least 3
(Manic)
Substance Withdrawal
Decreased level of alertness
Unawareness
Lethargy
Slowed speech or movements
Staring
Apathy
Both features
Most common
Hypervigilance/ irritability
Restlessness
Fast or loud speech
Combativeness
Impatience
Swearing, singing, laughing, anger Uncooperativeness, euphoria, wandering,
Easy startling,
Fast motor responses,
Distractibility, tangentiality
Nightmares
Persistent thoughts

10. History/ROS Comprehensive History preferred if possible
A broad range of common causes of delirium
Recent febrile illness- infection
PMH, Surgery, Hospitalization
Thorough Medication list- 30% of the cases
Social hx- alcohol or drug abuse
Recent depression/ psychiatric problems
ROS- behavioral, neural review for delirium
All others- underlying causes:

11. PE Looking for underlying causes
Vital signs- fever- infection, tachycardia- alcohol withdrawal, fever & tachycardia- anticholinergic toxicity
General appearance- jaundice with hepatic failure
HEENT- cherry-red lips with CO poisoning, bitten tongue with convulsive seizure
C/V – cardiac issues?
GI/GU- Liver failure? UTI?
Skin- burns?
Neurologic exam- Attention, Alertness, Cognitive function for delirium

12. Diagnostic Tests The Confusion Assessment Method (CAM)
Standard test to diagnose delirium
11 questions in 5 minutes
94-100% Sensitivity, % Specificity
First 2 sets + either one of last 2 sets
Onset and fluctuating course
Inattention
Disorganized thinking
Altered level of consciousness
Other tests – multiple tests are considered when testing for primary causes: CBC, urinalysis, blood gas, Vitamin B12, LFT, CXR, head CT, EEG, Lumbar puncture, … MRI is rare.

13. The Confusion Assessment Method

14. Differential Dx
Dementia: insidious onset, chronic, not much fluctuation, intact alertness and attention
Mania: Intact cognitive function, not usually disoriented, longer history
Depression: not much fluctuation, gradual onset with longer history, intact cognitive function,
Schizophrenia: rarely after 50, auditory > visual hallucination, relative less fluctuation throughout a day
Nonconvulsive status epilepticus: under-recognized seizure. EEG required.
Brain lesion- Imaging required.

15. Treatment Non-pharmacological Tx Treat the underlying condition
Re-orientation with a calendar or a clock
Cognitive stimulation with family and friends
Decrease the number of staff and minimized change
Adequate hydration, nutrition, oxygen supply

16. Pharmacological Tx Antipsychotic
Haloperidol mg IM; observe after min and repeat as needed / mg PO BID, and q 4hrs prn
First line med
Atypical antipsychotics
Olanzapine (Zyprexa) 2.5mg once daily PO
Quetiapine (Seroquel) 25mg BID PO
Risperidone (Risperdal) 0.5mg BID PO
Benzodiazepine
Lorazepam (Ativan) mg q 4hrs PO prn
Antidepressant
Trazodone 25 – 150mg PO at bedtime

17. Recommendations American Geriatric Society
Do not use benzodiazepines or other sedative-hypnotics in older adults as first line for insomnia, agitation, or delirium.
Avoid physical restraints to manage behavioral symptoms to older adults with delirium.
American Psychiatric Association
Do not prescribe antipsychotic meds for any indication without appropriate initial evaluation and ongoing monitoring.

18. Prognosis Generally poor outcome especially with hypoactive delirium
Prolonged hospitalization
Functional impairment
Psychological stress
Institutionalization
Long-term cognitive impairment
Increase costs
Death
Full recovery

19. References
Ali, S., Patel, M., Jabeen, S., Bailey, R. K., Patel, T., Shahid, M.,…Arain, A. (2011). Insight
into delirium. Innovation in Clinical Neuroscience, 8(10). Retrieved from
Francis, J. (2014). Delirium and acute confusional states: Prevention, treatment, and
prognosis. UpToDate. Retrieved from
Francis, J., & Young, G. B. (2014). Diagnosis of delirium and confusional states. UpToDate.
Retrieved from
Grover, S., & Kate, N. (2012). Assessment scales for delirium: A review. World Journal of
Psychiatry, 2(4). doi: /wjp.v2.i4.58
Kalish, V. B., Joseph, E. G., & Unwin, B. K. (2014). Delirium in older persons: Evaluation
and Managemet. American Family Physician, 90(3). Retrieved from