1. Delirium: Risk, Recognition and Management
Nick Dewan, MD

2. Disclosures: Nothing to disclose

3. Goals Understand clinical criteria for delirium
Overview general causes
Identify hypo-, hyperactive and mixed delirium
Identify patients at increased risk for delirium
Understand non-pharmacologic and pharmacologic treatment of delirium

4. Delirium in DSM-5
A. Disturbance in attention (reduced ability to direct, focus, sustain and shift) and awareness (reduced orientation to the environment)
B. Develops over a short period of time (usually hours to days), represents a change from baseline, tends to fluctuate during the course of the day.
C. Additional disturbance of cognition (memory deficit, disorientation, language, visuospatial ability or perception)
Disturbance in criteria A and C 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
Evidence from history, PE or laboratory findings that the disturbance IS a direct physiological consequence of another medical condition, substance intoxication or withdrawal, or exposure to a toxin, or is due to multiple etiologies.

5. Pathogenesis
Diffuse, reversible decrease in cerebral oxidative metabolism.
Hypotheses:
Acetylcholine believed to be the primary neurotransmitter mediating the dysfunction.
The reticular formation is a primary site of dysfunction.
Downstream increases in dopamine, serotonin, and glutamate.
Cytokines may contribute by increasing the permeability of the blood-brain barrier and altering neurotransmission.
Chronic stress increases cortisol and cytokines, both of which have been associated with delirium.

6. Why care?
Large amount of our patients suffer from it - up to 15% of hospitalized older adults, % of mechanically ventilated ICU patients
Presence of delirium portends worse outcome for patients
Possible long-term cognitive sequelae
Distressing to both patients and families

7. Why screen and/or treat?
Impact on quality metrics:
Reduce LOS
Reduce risk of injury - falls, pulling lines, requiring restraints
Reduce mortality and morbidity - short and long term
Reduce costs
Newer evidence showing delirium may be an independent risk factor for development of cognitive impairment/dementia even in those with no history of cognitive problems
PTSD symptoms from delirious episodes

8. Search for causes I WATCH DEATH Look for obvious first:
Alcohol/drugs - intoxication OR withdrawal
Polypharmacy
Metabolic derangements
CVA, infection, post-operative state
Uncontrolled pain

9. Remember these medications…
High risk
Medium risk
Low risk
Opioid analgesics
Alpha-blockers
ACE inhibitors
Antiparkinsonian agents (particularly anticholinergic agents)
Antiarrhythmics (lidocaine has the highest risk)
Antiasthmatics (highest risk with aminophylline and lowest risk with inhaled agents)
Antipsychotics (particularly sedating agents)
Antidepressants (particularly anticholinergic agents)
Antibacterials
b-Blockers
Quinolone
Digoxin
Anticonvulsants
Nonsteroidal anti- inflammatory drugs
Calcium channel antagonists
Benzodiazepines
Centrally acting agents
Diuretics
Postganglionic sympathetic blockers
H2-antagonists
Corticosteroids
Lithium

10. How to identify delirium
Quick and easy bedside assessment:
Confusion Assessment Method (CAM) and CAM-ICU, which takes into account Richmond Agitation-Sedation Scale
94-100% sensitive and 90-95% specific
When in doubt, can order EEG to assist
rule out non-convulsive status epileptics
some causes of delirium have characteristic EEG changes - metabolic encephalopathies, hepatic encephalopathy

11. 1. Acute onset and fluctuating course
Feature
Assessment
1. Acute onset and fluctuating course
This feature is usually obtained from a family member or nurse and is shown by positive responses to the following questions: 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
This feature is shown by a positive response to the following question: Did the patient have difficulty focusing attention, for example, being easily distractible, or having difficulty keeping track of what was being said?
3. Disorganized thinking
This feature is shown by a positive response to the following question: Was the patient's thinking disorganized or incoherent, such as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?
4. Altered level of consciousness
This feature is shown by any answer other than "alert" to the following question:: Overall, how would you rate this patient's level of consciousness? (alert [normal]), vigilant [hyperalert], lethargic [drowsy, easily aroused], stupor [difficult to arouse], or coma [unarousable])
The diagnosis of delirium by CAM requires the presence of features 1 and 2 and either 3 or 4.

12. Types of delirium
Hypoactive
Hyperactive
Mixed

13. Hypoactive Delirium Most prevalent but least often recognized
up to 80% of cases
Worse outcome than hyperactive or mixed as frequently missed due to lack of agitation/behavioral problems leading to longer duration
Characterized by psychomotor retardation, apathy, slowed speech, decreased alertness
Frequently mistaken for depression
remember impaired attention and disorientation as distinguishing features

14. Hyperactive and Mixed Types
Hyperactive is LEAST prevalent, but most frequently recognized due to increased agitation
from 6-46% of cases
Agitation, sleep disturbance, hyper vigilance, irritability, increased rate of speech, hallucinations, delusions
May be mistaken for psychosis and/or mania - increased suspicion if patient with only visual hallucinations; hallmark is picking at the air, seeing bugs
fluctuating levels of consciousness/alertness and inattention again distinguish from psychiatric origin
Any patient requiring physical restraint should be assessed for delirium
Mixed
from 18-55% of cases
alternating features of both hyper/hypoactive

15. At Risk Patients Age - Every year > 65 increases risk by 2%
History of dementia
Substance use history
Surgical procedure - vascular higher risk
ICU stay - huge increase with ventilated patients
Burns
Polypharmacy (>4 medications)
Immobility - restraint use
Hearing/Visual Impairment
Chronic mental illness

16. Why is age such a huge risk?
Decreased neuronal mass
Low level of neurotransmitters, due to decreased oxidative metabolism of the brain
Overall decline in cardiovascular and respiratory reserves leading to diminished O2 delivery to the brain
Slower drug metabolization and clearance
Co-existence of other medical illnesses and consequent polypharmacy

17. How to Treat Non-pharmacologic interventions first line!
Treat underlying cause - treat infection, d/c offending medications (benzos, anticholinergics, narcotics)
Frequent reorientation - date, location on white board, family at bedside if possible
Early mobilization
Remove restraints, catheters, lines
Provide assistive devices - glasses and hearing aids
Adhere to day/night cycles - blinds open, lights on daytime, lower light, decreased noise at night
In ICU, sedation holiday (evidence for use of Precedex over Versed, Propofol for decreasing delirium incidence)
Uncontrolled pain risk factor - non-opioids first if possible, avoid Demerol if using opioids
Manage family member expectations - key to overall stay

18. Managing expectations
Significantly disturbing for patients and families. If family actively involved, more time spent up front can alleviate anxiety and garner a greater understanding of process
DO NOT promise improvement, or return to baseline, particularly in elderly patients - realistic expectations are key
Discuss in terms of likelihood of recovery, possibility of improvement and emphasize that everything possible will be done to assist
If conversation held with family as soon as delirium is noticed, reduces perception that patient is being discharged “too soon” or that “not enough was done” if patient is still delirious upon discharge

19. Pharmacologic Treatment
Last resort but frequently necessary to control agitation
No good evidence for cholinesterase inhibitors
Antipsychotic agents still mainstay
No agent, either antipsychotic or not, is FDA approved for delirium treatment
Haldol still first choice due to length of experience with medication - preferably IV to reduce risk of EPS, increase rapidity of onset, 2x as potent as oral form
2-2.5mg for mild agitation, 5mg for moderate, mg for severe agitation
Severe agitation can double dose q30min until calm but rousable to voice
Expectation of staff is for immediate effect, but should expect at least 30 min for improvement
Elderly 1/3 lower dose
Varying studies on benefit for Haldol prophylaxis in high risk patients, but not currently recommended to administer for prophylaxis as no robust, consistent evidence

20. Pharmacologic Treatment
Atypical antipsychotics gaining favor, show equally efficacy to Haldol for the most part
Studies with Risperdal, Seroquel, Zyprexa and Geodon
Zyprexa may not be great for those older than 75 (possibly due to increased anticholinergic activity)
Positives and negatives - less risk of EPS, varying risk of QTc prolongation (still present with Haldol as well)
No IV forms, only oral or IM
Risperdal and Seroquel with no IM formulations
Risperdal and Zyprexa have ODT that make oral admin easier
Seroquel better in agitation with Parkinson’s and Lewy Body Dementia patients but nothing is great
Do NOT administer Zyprexa IM in conjunction with benzo - risk of respiratory suppression and death
Know your most common side effects
Risperdal - stiffness, mild sedation; Seroquel - hypotension and profound sedation; Geodon - akathisia and QTc prolongation; Zyprexa - hypotension and profound sedation

21. QTc Prolongation
Monitor daily and consider to discontinue if QTc >500ms, >60ms change or >25% change from baseline. Check for other offending agents!

22. Role of Benzodiazepines
Really only for patients with delirium related to substance withdrawal
Alcohol and benzos - high index of suspicion in someone who presents with elevated vitals, temp, hallucinations and no obvious signs/etiology of infection
Can worsen sedation and delirium in patients with other etiologies
Study comparing Haldol, Chlorpromazine and Lorazepam in treatment had to d/c Lorazepam arm due to active harm
Administration of benzos an independent risk factor for development of delirium
Quicker onset than antipsychotics leads to continued use and reliance for treatment of non-withdrawal related delirium despite drawbacks
Useful when delirium leads to catatonic symptoms - under recognized

23. Post Hospitalization
Older the patient, the longer the delirium, longer it takes to recover - if at all
8 fold increase in risk of incident dementia
Increased rate of placement at SNF/ALF
Increased mortality -
One month 14% increase in mortality
Six month 22% increase in mortality

24. Take Aways Delirium very prevalent, frequently not recognized
Increases morbidity, mortality, cost, LOS both in short and long term
Risk of development of new cognitive problems or worsening of previously existing cognitive problems
Non-pharmacologic treatments and management of family expectations are key
Pharmacologic treatments last resort but antipsychotics remain mainstay of treatment

25. Resources
Cole MG, Primeau FJ. Prognosis of delirium in elderly hospital patients. CMAJ ; 149(41).
Inouye, S., van Dyck, C., Alessi, C., Balkin, S., Siegal, A. & Horwitz, R.. Clarifying confusion: the confusion assessment method. Annals of Internal Medicine ; 113(12),
Diagnostic and Statistical Manual of Mental Disorders Fifth Edition
Davis, D., Muniz Terrera, G., Keage, H., et al. Delirium is a strong risk factor for dementia in the oldest-old: a population based-cohort study. Brain ; 135:
Fong, T., Daivs, D., Growdon, M., et al. The Interface of Delirium and Dementia in Older Persons. Lancet Neurology August; 14 (8):
Al-Qadheeb, N., et al. Preventing ICU Subsyndromal Delirium Conversion to Delirium with Low Dose IV Haloperidol: A Double Blind, Placebo-Controlled Pilot Study. Critical Care Medicine March; 44(3):
van den Boogaard, M., Schoonhoven, L., et al. Haloperidol prophylaxis in critically ill patients with a high risk for delirium. Critical Care ; 17: R9.
Barr, J., et al. Clinica Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Critical Care Medicine. 2013; 41:
Page, V., Efficacy of Intravenous Haloperiod on the duration of Delirium and Coma in Critically Ill Patients (Hope- ICU): a Randomized, Placebo-Controlled Trial. Lancet Respiratory Medicine September; 1(7):
Parker, R., et al. Dexmedetomidine for the treatment of hyperactive delirium refractory to haloperidol in non- intubated patients. Journal of Thoracic Disease ; 8(7): E
Yoon, H., et al. Efficacy and safety of haloperidol versus atypical antipsychotic medications in the treatment of delirium. BMC Psychiatry ; 13: 240.
Girard, T., et al. Feasibility, Efficacy, and Safety of Antipsychotics for ICU Delirium: the MIND Randomized, Placebo- Controlled Trial. Critical Care Medicine February; 38(2):
Inouye, S. Delirium in older persons. New England Journal of Medicine ; 354:
Brietbart, W., et al. A double-blind trial of haloperidol, chlorpromazine and lorazepam in treatment of delirium in hospitalized AIDS patients. American Journal of Psychiatry February; 153(2):