1. Delirium in Older Adults
Kathleen Pace Murphy, PhD, MS, GNP-BC
Assistant Professor, UTHealth Division of Geriatric and Palliative Medicine
Deputy Director, Consortium on Aging

2. Kathleen Pace Murphy, PhD, MS, GNP-BC Assistant Professor, UTHealth Medical School Division of Geriatrics and Palliative Medicine Deputy Director, Consortium on Aging
Neither I nor members of my immediate family have any financial relationship with commercial entities that may be relevant to this presentation.

3. Delirium Incidence 10-24 percent of the hospital patient population
Incidence increases with patient complexity
60 percent occurs in older adult patients
60-80 percent incidence in those admitted to a Medical ICU
80-90 percent in older adults with terminal cancer.
Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis and treatment. Critical Care Clinics ;24: /

4. Delirium or Acute Confusional State DEFINITION
Syndrome
Acute Brain Failure
Characterized by:
Acute
Disturbance in consciousness
Reduced ability to focus, sustain or shift attention
Occur over short period of time
Fluctuates over the course of a day
Known by multiple names: acute confusional state, acute mental status change, organic brain syndrome, reversible dementia
Predictor for future cognitive and functional decline
TO DISTINGUISH BETWEEN DELRLIUM, DEMENTIA, AND DEPRESSION, THE CLINICIAN MUST ASCERTAIN THE PATIENT’S BASELINE STATUS AND THE TIMEFRAME OF COGNITIVE CHANGES.

5. Etiology Potential causes of delirium include: Inadequate pain control
Drug or toxin
Metabolic disorders
Neurovascular insult
Systemic organ failure
Complications from a systemic disease

6. Figure out the trigger
Drug use (hypnotics, anticholinergic) (30%) Electrolyte abnormalities (40%) Lack of drugs (withdrawal) Infection (40%) Reduced sensory input (24%) Intracranial problems (stroke) Urinary retention and fecal impaction Myocardial or metabolic problems (14- 26%)
Notes:
Most patients are particularly prone to medication –induced delirium because there are a number of contributory medications. Medication-induced delirium is observed in both hospitalized patients and nonhospitalized patients.
Drugs – any new additions, increased dosage, or interactions; consider OTC and alcohol, high-risk drugs, lack of drugs, withdrawal from chronically used sedatives,
Electrolyte abnormalities – especially dehydration, sodium imbalance,
Infection – respiratory skin and UTI
Reduced sensory input – poor vision, poor hearing, use of restraints, bed bound status
Intracranial - rare – consider only if new focal neurologic findings or suggestive history, or dx evaluation – infection, hemorrhage, tumor or stroke
Urinary, fecal – urinary retention (cystocerebral syndrome), fecal impaction, urinary catheter
Myocardial, pulmonary, metabolism – MI, arrhythmia, exacerbation of CHF, COPD, hypoxia, thyroid
Surgery – 15% after elective noncardia surgery, up to 50% after cardiac bypass, AAA or hip fx repair
Often combination of several of the above.
Francis J, Martin D, Kapoor W: A prospective study of delirium in hospitalized elderly. J Am Med Assoc. 263:  1990

7. Delirium Increased mortality Poorer functional status
Limited rehabilitation
Increased hospital-acquired complications
Prolonged hospital stay
Increased risk of institutionalization
Higher health care expenditures.
NOTE:
Those who experience delirium may also exhibit adverse effects, such as aspiration, loss of independence, or decreased mobility.
Although delirium frequently goes unrecognized in hospital settings, about 20% of all patients 65 years and older are affected (Maldonando, 2008).
When delirium is not recognized in a hospital setting, patients often face extended stays, increased complications, higher transfer rate to nursing homes, and more dependence on care after discharge.

8. Differential Diagnosis
Hypoactive Delirium
Hyperactive Delirium
Mixed Delirium (46%)
**The main feature differentiating delirium from depression from dementia:
Acute – fluctuating nature of symptoms
NOTES:
Because delirium is often misdiagnosed as dementia or another type of acute confusion, treating it requires determining the underlying cause of confusion.
Generally, delirium has more than 1 cause and may present as different types
The symptoms can mimic other medical conditions, most commonly dementia, depression, AD, or schizophrenia.
Mixed delirium – is now the most common type of delirium, in which often presents as a waxing and waning pattern of agitated and combative behavior mixed with drowsy and hypoactive behavior.

9. Delirium Differential Diagnosis
Depression
Delirium
Dementia
Onset
Weeks to months
Hours to days
Months to years
Mood
Low Apathetic
Fluctuates
Course
Chronic, Responds to treatment
Acute, responds to treatment
Chronic, with deterioration over time.
Self-awareness
Likely to be concerned about memory
Maybe aware of changing cognition
Hide or be unaware of memory
ADLs
May neglect basic self-care
Intact or impaired
Intact early, impaired as disease progresses
IADLs
Intact early, impaired before ADLs as disease progresses
Sarutzki-Tucker & Ferry, 2014

10. Clinical Presentation
Clinical manifestations appear over a shorter period of time (few days)
Progressive decline in memory, awareness to surroundings or behavior
Fluctuate throughout the day
Inability to maintain normal sequential thought

11. PATHOPHYSIOLOGY Pathophysiology is unclear
Widespread derangement of cerebral metabolism or cerebral insufficiency that leads to decreased synthesis of cerebral neurotransmitters, especially acetylcholine.
Brain maladaptive reaction to acute stress (Ham et al, 2014)
The core group of clinical manifestations:
Attention deficits
Sleep-wake cycle disturbance
Motor activity changes
May present as psychosis, mood changes, fluctuating LOCs, disorientation, memory impairment, and disturbances in speech and language.

12. MORTALITY Delirium is a medical emergency
Persons who have delirium have a statistically significant higher risk of death compared to age cohorts who do not.

13. Medication Hierarchy Level 1 - Neuroleptic Level 2 - Level 3
Level One - Neuroleptics
Level Two – Analgesics; Sedatives-Hypnotics; Dopamine agonists
Level Three – Antihistamine; anti-inflammatory; anticholinergic; antidepressants; cardiac glycosides
Level Four – H2 Antagonist, Dihydropyridine; Tricyclic antidepressants; anti-Parkinson; antimicrobials
NOTES:
Studies estimate that 12=39% of delirium cases stem from a patient’s medication.
Virtually any medication can cause delirium in an at risk elderly patient.
Even previously tolerated medications may pose potential risk when the person is acutely ill or as the person ages.
Several medications across the drug spectrum have been found more likely to exacerbate delirium, including prescription, OTC, complementary and illicit drugs.
The table above adapted from Gatewood, Clegg and Young and Catic provides a hierarchy of medications that are attributed to delirium

14. ANTICHOLINGERGIC MEDICATIONS Play a major role in delirium development
Score 3- High ACA
Score 2 – Moderate ACA
Score 1 – Mild ACA
Amitriptyline
Amantadine
Alprazolam
Atropine
Belladonna
Atenolol
Clozapine
Carbamazepine
Bupropion
Darifenacin
Cyclobenzaprine
Captopril
Desipramine
Cyproheptadine
Chlorthalidone
Diphenhydramine
Loxapine
Cimetidine
Doxepin
Meperidine
Clorazepte
Hydroxyzine
Methotrimeprazine
Codeine
Imipramine
Molindone
Colchicine
Nortriptyline
Oxcarbazepine
Diazepam
Olanzapine
Pimozide
Digoxin
Oxybutynin
Fentanyl
Paroxetine
Furosemide
Quetiapine
Haloperidol
Tolterodine
Metoprolol
Prednisone
ANTICHOLINGERGIC
MEDICATIONS
Play a major role in delirium development
Cumulative anticholinergic burden
**ACA= anticholinergic activity
Lecture Notes:
The concept of total anticholinergic burden – cumulative anticholinergic activity –
Based on recent evidence, each definite anticholinergic drug increases the risk of cognitive impairment by 46% over 6 years
Each one point increase in the anticholinergic burden score, there is a decline in MMSE of 0.33 points over 2 years, and a 26% increase in the risk of death.
Campbell N, Boustani M, Lane K, et al.: Use of anticholinergic and the risk of cognitive impairment in an African-American population. Neurology. 75:  
Fox C, Richardson K, Maidment, et al.: Anticholinergic medication use and cognitive impairment in the older population. The Medical Research Council Cognitive Function and Ageing Study J Am Geriatr Soc. 59 (8):  2011 Aug 

15. Screening Tools Richmond Agitation Sedation Scale (RASS)
Confusion Assessment Method (CAM)
Confusion Assessment Method for ICU (CAM-ICU)
Neelon and Champagne Confusion Scale (NEECHAM)
NOTES:
Assessment tools are helpful to directly test the patient’s cognitive performance level; however, results vary with the patient’s age, educational level, ethnicity and language.
It is important for the person using the assessment tool to know the patient’s baseline mental status.
Each type of assessment has its won advantages and disadvantages.
Determining the most appropriate assessment tool is largely based on on the psychometrics of the tool, feasibility of the scale, the patient’s amenability to being tested, the clinical setting and the need for a diagnostic tool versus a monitoring too.

16. NOTES:
A sedation assessment is an easy, cost-effective method to ensure a patient is not over sedated, which may lead to delirium.
One easy to use tool is the Richmond Agitation Sedation Scale (RASS).
Patient’s are evaluated on a Likert scale where 4+ represents a very combative, violent patient and -5 is a patient who is unarousable and does not respond to voice or physical stimulation.
This tool uses observation as well as verbal and physical stimulation to determine a patient’s sedation level.

17. E. Wesley Ely, MD MPH and Vanderbilt University, 2002.
NOTES:
Some of the most widely used tools today are CAM and the CAM-ICU.
The CAM-ICU:
Engages those caring for the patient to evaluate for delirium by first subjectively evaluating if there has been a change or fluctuation in a patient’s baseline mental status.
If such as change is detected, the evaluator continues the assessment by asking the patient to squeeze the evaluator’s hand each time a specific letter is spoken while the evaluation reads a sequence of letters, if the patient has 2 or more errors
Continue the assessment by evaluating the sedation level of the patient (RASS)
Next, patient is screened for disorganizae3d thinking by responding to a series of simple commands or answering simple yes/no questions.
Both the CAM and the CAM –(CU have shown sensitivity of 94% to 100% and a specificity of 89% to 95%.
This high sensitivity (true-positive) and high specificity (or true-negative) rate allow the provider confidence in distinguishing delirium from other differential diagnoses when the CAM scale is used on a regular basis.
E. Wesley Ely, MD MPH and Vanderbilt University, 2002.

18. Confusional Assessment Method (CAM) Delirium if you have 1 + 2 +[either 3 or 4].
Diagnostic Features
Definitions and Characteristics
1. Acute Onset
Fluctuating Course
Is there evidence of an acute change in mental status from baseline?
Did the abnormal behavior fluctuate during the day, does it come and go, or increase and decrease in severity?
2. Inattention
Did the patient have difficulty focusing attention (easily distracted) or have difficulty keeping track or what was being said?
3. Disorganized Thinking
Was the patient’s thinking disorganized or incoherent, e.g. rambling, irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?
4. Altered LOC
LOC – alert (normal), vigilant (hyper alert), lethargic (drowsy but easily arousable), stupor (difficulty to arouse) or coma (unarousable)
MMSE/SLUMs no value
Inouye SK, vanDyck CH, Alessi CA, et al. Clarifying confusion: The Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med 1990:113:941-8.

19. NOTES:
The Neelon and Champagne Confusion Scale (NEECHAM) is used to assess for delirium in patients
The NEECHAM scale has a sensitivity of 87 % and specificity of 95% and incorporates the level of processing information, level of behavior, and the physiological condition.
It calculates a total score based on each category to determine a level of confusion, if any.
It is easy to use with minimal instruction to those caring for the patient.

20. Delirium Management Listical
Knowledge and addressing the underlying cause
Be mindful of the environment
Do not over stimulate
Good patient care
Medications (hopefully last resort)
NOTES:
Knowledge and addressing the underlying causes
Be mindful of the environment ( minimize distractions, decrease noise, glasses, hearing aides put them in)
Sleep assessment (lack of sleep affects circadian rhythm and predisposes to delirium – earplug, eye masks, melatonin) Melatonin is a natural hormone which is produced by the pineal gland and released in response to light-dark cycles. It increases at night and decreases during the daylight hours. Adding melatonin to a person’s medication regimen at night assists in this rise, causing the patient to become less alert and drowsy.
Overstimulation can disorient patients an cause or aggravate delirium. Strategies – ensure clocks and calendars are visible to patient, communicate slowly, simple and calm manner. Playing light music's can soothe extremes in noise. Glasses and hearing aides are very helpful. Adequate light during the day and dimmed light at night to help with orientation and prevent confusion about time. Keep safe.
Always assess respiratory status and oxygenation, maintain hydration, evaluate for presence of cardiac damage or CVA ischemia.
Drug treatment – last resort – try non-pharmacologic management – IV haloperidol to help decrease agitation in patients with delirium because it works at the cerebral synapses and the basal ganglia by blocking dopamine-mediated neurotransmission facilitating stabilization of the cerebral function.
You cannot use this drug in patient’s with withdrawal syndrome, hepatic insufficiency, or neuroleptic malignant syndrome.
Other meds – atypical antipsychotics = second line of treatment. There is an increased mortality in older patients with dementia when using this class of medications that works by blocking cortical serotonergic receptors.
Lorazepam may be used only if the patient is going through alcohol or BZD withdrawal, has Parkinson disease or has a neuroleptic malignant syndrome.

21. Vital Signs: BP, P, HR, T, Pulse Ox, Pain Physical Examination
Assessment
Vital Signs: BP, P, HR, T, Pulse Ox, Pain
Physical Examination
Urinalysis
Cr, Na, K, Ca, Glucose
CBC with differential
Review old and new anticholinergic medications
Review old and new sedating medications
Review the need for Foley catheters, IV lines, and other tethers
Apply glasses, insert hearing aides
NOTES:
Laboratory values should be watched for electrolyte imbalance through CMP and monitoring for infection through a CBC.
Evaluate serum drug levels or urine toxicology screens for their medication levels and evaluate for overdose
Blood gases, thyroid function and vitamin B 12 levels may also be considered when looking for causative factors for delirium
4. Brain imaging or more invasive diagnostic test for delirium assessment are not indicated without the presence of positive findings during the history, physical examination or chart review.
5. Interprofessional assessment is a must
EEG: very helpful for delirium (diffuse, symmetric slowing) vs dementia (normal to moderate dementia) vs depression (normal, unless getting benzos)

22. Intervention Step 1 Identify and Treat reversible contributors
Medications
Infection
Fluid balance disorders
Impaired CNS oxygenation
Severe pain
Sensory deprivation
Elimination Problems
Medication – reduce or eliminate offending medications, or substitute less psychoactive medications
Infections – treat common infections –urinary, respiratory , soft tissue
Fluid balance disorders – Assess and treat dehydration, heart failure, electrolyte disorder
Impaired CNS oxygenation – treat anemia, hypoxia, hypotension
Severe pain – assess and treat, use local measures and schedule pain regimens that minimize opioids; avoid Demerol
Use eyeglasses, hearing aid, portable amplifier, clear cerumen
Elimination problems – assess and treat urinary retention and fecal impaction, prevent constipation

23. Intervention Step 2 Maintain behavioral control
Behavioral interventions
Pharmacologic Interventions
Necessary for behavior that is dangerous to patient or others and does not respond to other management strategies
Encourage family visitation

24. Intervention 3 Anticipate and prevent or manage complications
Urinary incontinence
Immobility and falls
Pressure ulcers
Sleep disturbance
Feeding disorders
Urinary incontinence – implement scheduled toileting program
Immobility and falls – avoid physical restraints; mobilize with assistance; use PT
Pressure ulcers – mobilize, reporisiton immobilized patient frequently and monitor pressure points
Sleep disturbance – implement a nonpharmacologic sleep protocol; avoid sedatives
Feeding disorder – assist with feeding; use aspiration precautions

25. Intervention 4 Restore function in delirious patients
Hospital environment
Cognitive reconditioning
Ability to perform ADL
Family education/support/ participation
Discharge
Hospital environment – reduce clutter and noise especially at night; provide adequate lighting, have familiar objects brought from home
Cognitive reconditioning – have staff reorient patient to time, place, person at least 3 times per day
Ability to perform ADL- As delirium clears, match performance to ability
Family education/support/participation – provide education about delirium, its causes and reversilitiy, how to interaction and family’s role
Discharge – Because delirium can persist, provide for increased ADL support; follow mental status changes as barometer of recovery

26. Prevention Limit use of medications known to cause delirium
Ensure good nutrition and hydration
Correct sensory deprivation
Encourage normal sleep patterns
Promote cognitive stimulation

27. Prognosis Delirium is usually reversible.
Take several weeks for mental function to return to normal levels
The longer the delirium goes untreated – there is worsening global cognition and executive function worsening.
Pathophysiological evidence – inflammation – neuronal apoptosis – brain atrophy
NOTES:
A recent study found delirium to be associated with inflammation and neuronal apoptosis, which may lead to brain atrophy. As opposed to cerebral atrophy as previously thought.
Studies vary on precisely when morbidity and mortality begin to increases if symptoms persist; most agree that if delirium persists; and mortality begins to increase if symptoms persist;
A 2009 study showed patients with unresolved delirium were 3 times more likely to die within 1 y ear compared with patients whose delirium was resolved.

28. References
Catic AG. Identification and management of in-hospital drug-induced delirium in older patients. Drugs Aging :28(9):
Clegg A, Young JB. Which medications to avoid in people at risk of delirium: a systematic review. Age and Ageing :23-29.
Gatewood M. Managing delirium among elderly patients in the ED. Physician’s Weekly, 2013.
Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis and treatment. Critical Care Clinics ;24:
Reade MC, Finfer S. Sedation and delirium in the intensive care unit. New England Journal of Medicine 2014;370(5):
Sarutzki-Tucker A, Ferry R. Beware of delirium. The Journal for Nurse Practitioners 2014:10(8);