Delirium: Underrecognized,

Undertreated and Deadly

Coleman Foundation Winter Workshop

February 28, 2013

Andrea Bial, MD

Joanna Martin, MD

Objectives

Learning Objectives

1.  Understand how to recognize delirium in the hospice and palliative setting.

2.   Be able to identify possible factors contributing to patients’ delirium.

3.   Incorporate best evidenced-based medicine in treating delirium in hospice and palliative care settings.

 

Content Bullets

1.    Recognize agitation, confusion, altered level of consciousness, hallucinations, restlessness and other behaviors associated with delirium in patients with advanced chronic illness.

2.    Understand when to pursue reversible causes of delirium and when to forgo evaluation and focus on comfort.

3. Be able to use both pharmacological and nonpharmacological interventions to treat delirium in patients with advanced chronic illness.

Delirium: What’s Going On?

Pathophysiology not well understood

Thought to be deficit of acetylcholine (e.g., anticholinergic drugs as precipitant) and/or excess of dopamine (that’s why levodopa can cause & Haldol can help)

Other neurotransmitters (GABA, serotonin, norepinephrine, melatonin, others) and cytokines may also be involved.

Inouye 2006; Irwin 2013

Delirium: Prevalence

~¼ to ½ of advanced cancer patients admitted to the hospital have delirium.

85-90% of all patients experience delirium in the hours or days before death.

Very common in hospitalized older patients 33% presenting to ER

14-24% on admission

15-53% post op

70-87% ICU

Inouye 2006;LeGrand 2012; White 2007

Delirium: Prevalence in Palliative Care

2013 Literature Review in Palliative Medicine: 13-42% prevalence at admission to palliative or hospice

units

26-62% prevalence at some point during hospitalization (in palliative or hospice unit)

Delirium: Outcomes

Increased hospitalized mortality (25-75%)

Increased 1-year mortality (40%)

Increased LOS (2x)

Increased hospital complications (incontinence, falls, pressure sores)

Increased institutionalization (2-3x)

Increased healthcare costs (STAT)

Irwin2013

Delirium: Recognition

Early identification of risk factors can reduce occurrence.

Early recognition of delirium can reduce duration (and potentially identify causative/contributing factors).

FOR LEARNERS: Lecture format adequate for knowledge about delirium, but

not to change provider behavior or improve outcomes.

Need interactive sessions and leaders using clinical pathways and assessment tools.

Inouye1993, Yanamadala2013

Why is delirium overlooked?

Fluctuating nature

Overlaps with dementia

Lack of formal cognitive assessment

Under appreciation of clinical consequences

Not considering the clinical diagnosis important

Types of Delirium

Hyperactive: “Agitated;” repeated (purposeless) limb movements,

restless, trying to get out of bed, hallucinations,….

Hypoactive Quite, withdrawn; may give monosyllabic answers to simple

questions, follow simple commands

Mixed

Predisposing Risk Factors

UPON ADMISSION

Serious illness (advanced cancer, sepsis, acute kidney failure,…)

Cognitive impairment

Vision impairment

Elderly

AFTER ADMISSION

Physical restraints

≥3 medications added

Malnourished

Urinary catheter placed

Inouye1993;1996;1999

An Ounce of Prevention…

Yale Delirium Prevention Trial : Orientation for cognitive impairment

Early mobilization

Prevention of sleep deprivation/fragmentation

Address vision & hearing impairments

Preventing dehydration

Inouye 1999

Overlooked

Inconsistent use of terminology (“confused, altered mental status agitated, lethargic,…”)

Objective testing rarely done

Confused with depression or dementia (see next slide)

Increase the risk of being overlooked: Hypoactive form

Fluctuating symptoms

Age ≥80yrs

del Fabbro2006

Identifying Delirium

Several tools available Confusion Assessment Method (CAM) (94-95% sens/spec)

Delirium Rating Scale

Delirium Symptom Interview

Memorial Delirium Assessment Scale

Casarett2001

CAM

1. Inattentive AND

2. Acute Onset w/ Fluctuating Course AND

3. Disorganized Thinking AND/OR

4. Altered Level of Consciousness

HAVE TO HAVE #1 & #2 AND THEN #3 AND/OR #4 for positive screen.

HINT: IADL

Inouye1990

CAM: example questions

1. Inattentive: repeat numbers, days of week/months of the year backwards OR observe staring into space, not keeping track of conversation, etc.

2. Acute/fluctuating: ask pt about confusion OR observe variations in attention, speech, thinking, or pyschomotor activity. (can also ask RN or family)

3. Disorganized thinking: what type of place is this, why are you here, see or hear anything unusual? OR observe if pt disoriented or uses illogical ideas/inappropriate words/rambling conversation.

4. Altered Level of Consciousness: falling asleep during interview, stuporous/comatose, non-communicative?

Huang2012

Evaluation (after Identification)

In hospitalized patients: History (does pt have dementia? What has been the time

course?)

Physical Exam (new wounds, neurologic deficits, urinary or fecal retention, new fx,…?)

Laboratory Tests (if none recent: wbc, cmp, TSH, B12?)

Radiology Tests (CXR, head CT,….?)

In palliative (Advanced, Chronically ill) patients, is this terminal restlessness?

Inouye2006

DELIRIUM

Evaluation

History (dementia?) andPhysical Exam(head to toe)

FOCAL EXAM:Do appropriate nextstep (e.g.,fevercx)

THEN, review meds& Order other tests

Treat Findings &Manage symptoms

NON-FOCAL EXAM:Review meds

Order addn’l tests

Treat Findings & Manage symptoms

Management

NON-AGITATED PATIENT:

Non-Pharmacologictreatment

AGITATED PATIENT:

Non-Pharmacologic& Pharmacologic tx

Palliative Patients Irwin2013

Evaluation in Palliative Patients

Need to address Goals of Care as it will guide extent of evaluation.

Easily addressed: constipation, urinary retention, medication side effect, dehydration

More likely to be reversible in younger patients, those without organ failure, and those w/ less cognitive disturbance.

May be shorter time until death in those w/ irreversible delrium.

Leonard2008

Delirium=Syndrome

Delirium is almost always multifactorial

Need to identify potential causes

Evaluation and treatment is always dependent on GOC

Causes of Delirium

1. Medications New drug

Dose too high

In withdrawal (e.g., benzodiazepines, psych drugs…)

2. Infection

3. Dehydration

4. Metabolic Abnormalities

Irwin2013;LeGrand2012

Additional Potential Causes of Delirium in CA pts

1. All of preceding causes, but also…

2. Primary or Secondary CNS tumors

3. Toxicity of antineoplastic therapies (chemo, xrt,…)

4. Toxicity of other drugs used in treatment (steroids, anti-nausea drugs, anticonvulsants,…)

5. Paraneoplastic neurological syndromes

Caraceni2005

Treatment: Underlying Cause

1. Adjust medication (if able) Any medication that has CNS s.e. can contribute to delirium

(especially those w/ hi anticholinergic activity)

See next slide

2. Treat infection

3. Address dehydration (IV fluids, sq fluids, oral hydration)

4. Consider fixing electrolyte abnormalities

Medications as Cause

Antibiotics Steroids

Benadryl NSAIDS

Benzos H2 Blockers

Digoxin Parkinson’s drugs

GI (Reglan, Bentyl) Tricyclics

Lithium

Narcotics

Neuroleptics

Any drug with anticholinergic properties!

Treatment: Nonpharmacologic

Safety of room (minimize bed rails or pad, lower bed, mats on floor)

Reorientation (verbal cues, date boards, shades up)

Reduce restraints (“official” and “unofficial”)

Family/friends at bedside

Supply glasses or hearing aids if appropriate

Treatment: Pharmacologic Caveats

NO MEDICATIONS are currently approved by the FDA for management of delirium

NO published DB, RCT to guide medication management of delirium.

NO consensus: oncology, geriatrics, psychiatry, palliative medicine

Goal is to maximize safety

Treatment: Pharmacologic

Haloperidol as first drug of choice Can be given IV, IM, SC, PO (pill or liquid)

LOW dose to start (0.5mg IV Q6H prn)

BEWARE EPIC!

Can repeat at 30mins if needed

Irwin2013;LeGrand2012

Haloperidol

Old, cheap, decades of use

Recent trial: 14 centers/4 countries/119 patients w/ delirium in hospice or palliative care: Average daily dose: 2.1mg

Most frequent s.e.: somnolence (9%) & urinary retention (5%)

1/3 had net benefit (NCI delirium score)

Risks present with ALL antipsychotics Black box warning on all: increased CV or infectious mx

when used in dementia-related psychosis

Crawford2013, Irwin2013

Other Pharmacologic Treatments

Other antipsychotics CAN be used Consider side effects: potentially WANT more sedation, or

weight gain, or other effect

May use if higher doses needed.

Benzodiazepines Can worsen delirium

Use as first-line only if alcohol/benzo withdrawal or having seizures

Can use as second line (in addition to Haldol) if not achieving adequate response

Delirium in the ICU

Estimates range from ~20-90% of patients

10% increase mx for each day of delirium

Additional risk factors: Coma

Sedatives

Neurologic diagnosis

Reade2014

Terminal delirium

Often referred to as “terminal restlessness”

Characterized by agitation, repeated nonsensical requests (“I need to sit up”), repetitive movements, picking at clothes and sheets.

Occurs in up to 85% of patients in the last weeks of life

Family/caregiver education is key

Can use Haldol first line for symptom management

Consider use of benzodiazepines if Haldol ineffective, especially in younger patients

Terminal delirium: Family Support

The experience of delirium for families can complicate bereavement

“Double loss” Grief when they lose ability to communicate meaningfully

with patient and again when the patient dies

Although previous care may have been excellent, if the delirium goes misdiagnosed or unmanaged, family members may remember a horrible death "in terrible pain”

Terminal Delirium: Family Support, contd.

Families may be ambivalent about medication use: want the pt to be comfortable, but fear lack of communication w/pt or worry that death is hastened.

Families should be given ample opportunities to ask questions; information may need to be repeated.

If suspect death is near, important to ask family if they want to know prognostic information.

Brajtman2005

Patient AB

105yo W in hospice w/ dementia and COPD.

Takes Xanax 0.25mg QHS (for years).

Called by RN: pt had a night of agitation: was up all night, convinced her son was being held hostage. When son was called to talk to her to reassure her he was ok, she was sure he was being forced to say he was fine.

CG couldn’t give her any more Xanax (pt refused) and family didn’t want to give her Haldol since last time she got it, “She was knocked out.”

Patient AB: Questions

Is this patient delirious?

Is this patient having terminal restlessness?

What do you recommend for the future? Increase bedtime Xanax

Repeat bedtime Xanax dose at start of agitation

Use Haldol anyway

Have son come over and sit w/ patient

Patient AB

What do you do?

1. Increase bedtime Xanax to 0.5mg.

2. Repeat bedtime Xanax dose at start of agitation.

3. Use Haldol anyway, starting at lower dose than before and use at start of agitation.

4. Have son come over and sit w/ patient.

5. 1., 2., 4.

6. 1., 3.

7. None of the above

Patient case #1

Mr. S is an 80 year old NH resident with history of end stage dementia admitted to hospice with history of aspiration pneumonia. Mr. S is usually calm, nonverbal and can sit in the dayroom in his wheelchair. The NH calls you that he has become quite agitated and won’t let the CNA give him his bath today.

Patient case #1 cont. . .

NH reports patient usually calm and often sits in day room, pleasantly confused at baseline.

Exam: VSS with no BM since hospice admission one week ago, patient lying in bed, agitated and moaning, lung exam stable, abdomen distended with bowel sounds; rectal vault filled with stool

Meds reviewed: HCTZ, Nifedipine, prevacid, roxanol 5mg q4hrs prn

Is this patient delirious?

Acute onset and fluctuating courseYES

Inattention YESDisorganized thinking NOAltered level of consciousness YES

Patient case #1

Patient is impactedFleets enema performed with good

resultsPatient straight cathed to check post

void residual which was <100ccMeds reviewed: HCTZ, nifedipine and

roxanol can cause constipationMeds adjustedBowel regimen: senna daily

Patient case #1

Patient much more comfortable by the next day

He returns to baseline within a few days

Hospice team provides a lot of oversight to nursing home care; patient requires close medication monitoring and has ongoing issues with constipation

Patient case #2

Patient is a 50 year old man with metastatic lung cancer admitted to hospice one month ago. Patient is steadily declining and using ativan now multiple times a day for anxiety. His wife contacts you that he is pacing, agitated and combative. At baseline he is usually anxious but can be reassured.

Case 2 continued. . .

On exam, he is confused, hyperalert and report seeing ants walking on the ceiling. He is unable to follow your other questions. His exam is remarkable for cachexia and hypoxia. SOB is controlled. Bowels are moving and patient urinating regularly.

Meds: ativan (7 doses in past 24 hrs), decadron 4mg, MS Contin 30 bid and roxanol 5mg prn

Is this patient delirious?Acute onset and fluctuating course

YESInattention

YESDisorganized thinking

YESAltered level of consciousness

YES

Patient case #2

Decision made to decrease dose of ativan back to bid and start haldol 0.5 mg bid and q4 hrs prn; give decadron in AM

Patient calms down enough to wear oxygen and wife able to manage sx

No need for opioid rotationEnds up using haldol 1mg q4hrs ATCMuch calmer and comfortable until death

one month later

Patient case #2

Decision made to decrease dose of ativan back to bid and start haldol 0.5 mg bid and q4 hrs prn; give decadron in AM

Patient calms down enough to wear oxygen and wife able to manage sx

No need for opioid rotationEnds up using haldol 1mg q4hrs ATCMuch calmer and comfortable until death

one month later

Patient Case #3

Patient is a 65 year old woman with stage IV breast cancer in home hospice

Family calls to report that patient more confused in past two days and sleeping more

Case #3 continued. . .

On exam: VSS, patient is sleepy and able to answer some questions but has trouble tracking conversation and is tangential, no focal neuro deficits noted, exam otherwise unchanged

Meds: fentanyl patch and roxanol prn; senna

Is this patient delirious?Acute onset and fluctuating course

YESInattention

YESDisorganized thinking

YESAltered level of consciousness

YES

Patient case #3 continued. . .

Patient with chronic severe pain so opioids not changed

Delirium likely due to final days of life

Family educated - KEY

Patient had some periods of lucidity over next several days and died a week later

Take Home Points

1. Be able to recognize signs and symptoms of delirium as early as possible; remember hypoactive is the most common form and often not found unless looked for.

2. Assess for easily reversible causes of delirium and understand when evaluation is not indicated due to terminal restlessness/near EOL.

3. Be comfortable in using both pharmacological and nonpharmacological measures to treat delirium. Provide information to family.

Works Cited BrajtmanS. Helping the family through the experience of terminal restlessness. JHosPallNurs 2005;7:73.

CaraceniA et al in Doyle D et al, eds. Oxford textbook of palliative medicine. OxfordUnivPress2005pp708-712

Cassarett D et al. Diagnosis and management of delirium at end of life. Ann Intern Med 2001;135:32

Crawford GB et al. Pharmacovigilance in hospice/palliative care: net effect of haloperidol in delirium. J Pall Med. 2013;16:1335-1341.

Del Fabbro E et al. Symptom control in palliative care—part III: dyspnea and delirium. J Pall Med. 2006;9:422-433.

Hosie A et al. Delirium prevalence, incidence and implications for screening. Pall Med 2013;27:486.

Huang LW et al. Identifying indicators of important diagnostic features of delirium. JAGS 2012;60:1044-1050.

Irwin SA et al. Clarifying delirium management: practical, evidence based, expert recommendations for clinical practice. J Pall Med. 2013;16:423-435.

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Inouye SK et al. Precipitating factors for delirium in hospitalized elderly persons: predictive model and interrelationship with baseline vulnerability. JAMA1996;275:852-857

Inouye SK et al. A multicomponent intervention to prevent delirium in hospitalized older patients. NEJM 1999;340:669.

Inouye SK. Delirium in older persons. NEJM 2006;354:1157.

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LeonardM et al. Reversibility of dellirium in terminally ill patients & predictors of mortality. PallMed2008;22:848.

Reade MC, et al. Sedation and delirium in the ICU. NEJM 2014;370:444

Von Gunten CF et al. New versus old neuroleptics: efficacy versus marketing. J Pall Med 2013;16:1509-1514.

White C et al. First do no harm…terminal restlessness or drug-induced delirium. J Pall Med 2007;10:345-351.

Yanamadala M et al. Educational intervention to improve recognition of delirium: a systematic review. JAGS 2013;61:1983-1993.