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Challenging Symptom Management:

Delirium, Agitation and


Shellie Williams, M.D.

University of Chicago Medicine

CE Provider Statements

Rush University Medical Center is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Rush University Medical Center designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s). Physicians should claim only credit commensurate with the extent of their participation in the activity.

Rush University is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. Rush University designates this live/internet enduring material activity for 1.0 Continuing Education credits.

CE Provider Statements & Conflict of Interest Disclosure

This activity is being presented without bias and without commercial support.

Rush University is an approved provider for physical therapy (216.000272), occupational therapy, respiratory therapy, social work (159.001203), nutrition, speech-audiology, and psychology by the Illinois Department of Professional Regulation. Rush University designates this live activity for 1.0 Continuing Education credits.

Disclosure of Conflict of Interest

This presenter has no conflict of interest to disclose.


Identify the common pathophysiology for challenging

symptoms in the palliative care patient.

Recognize predisposing and precipitating factors for

delirium in the palliative care patient.

Treat the distressing symptom of agitation associated with


Outline a treatment strategy for sleep disturbance in the

palliative care patient.

Mrs. A

75 yo widow with triple negative stage IV breast cancer (bone, brain mets). Recent xrt brain mets. Daughters note 3 day confusion, lethargy, withdrawn, not

sleeping. HR 110, furrow brow, dry mucosa, abdomen distended,

reaching in air, yelling for her deceased husband with periods of sedation. In ER 0.9 Nacl 125 cc/hr, hydromorphone 1mg iv for pain

and ativan 1mg for agitation. Home Decadron 6 mg bid, Fentanyl patch 50 mcg, Zofran 4 mg q 6 prn. Labs: bun/cr 50/1.4. UA sg 1.030, CXR LLL atelactasis,

KUB diffuse stool pattern. Her daughters tearfully watch her in a confused and

agitated state. What is happening? This is not our mother!

Challenging Symptoms: Delirium,

Agitation, Sleeplessness




Pathophysiology of Challenging Symptoms:

Tumor, AIDs,


Somatic Nerves Autonomic Nerves

Tumor byproducts

Metabolites: urea, Nh3,


Brain Function






Host Immune


J Pall Med 06:9 (2): 391-408 J Pall Med 06:9(2):391-408

Delirium: Defined, DSM-V Disturbance of consciousness (ie, reduced clarity of

awareness of the environment) with reduced ability to focus,

sustain, or shift attention.

Change in cognition (eg, memory deficit, disorientation,

language disturbance, perceptual disturbance) not better

accounted for by a preexisting or established dementia.

The disturbance develops over a short period (usually hours

to days) and tends to fluctuate during the course of the day.

Evidence from the history, physical examination, or lab

findings is present that indicates the disturbance is caused

by a direct physiologic consequence of a general medical

condition, intoxicating substance, medication or other


Delirium: Prevalence

22%-44% palliative care unit patients at admission

50% advanced cancer patients

68%-90% palliative care patients 30 days prior to death

Reversible in 50% palliative population

1. Leonard M, etal. J Psychosom Res. 2008 Sep;65(3):289-98 2. Morita T, etal. J Pain Sympt Manage 2007;34:579-589

Delirium: Morbidity/Mortality

Life threatening diagnosis

10-26% Higher Mortality

22-76% Increased rate death months post hospitalization

Excess rates Caregiver Stress

Leading cause for Palliative Sedation requests

J Psycho Som Res 2008 J Pain Sym Man 2011; 26 (2) 97-109

Delirium: Pathophysiology

Neurotransmitter Theory:

Cholinergic deficits: benadryl, scopalmine

Norephinephrine excess: antidepressants

Dopamine excess: anti-parkinson meds, anti-psychotics

Cytokines-IL1, IL2, TNF

Cerebral Hypoxia

Stress related hormonal changes

Delirium: Predisposing Factors

Advanced Cancer/Terminal diagnosis

Opioid Therapy

Multiple co-morbidities

Cognitive Impairment

Surgical need

Renal/Hepatic Impairment

Sensory Impairment

Imminent Dying

Advanced Age

Lawlor, P. JAMA, 2000; 284(19): 2427-29

Delirium: Precipitating Factors



Metabolic Disturbances



Untreated pain

Environment: ICU, changes


Delirium: Presentation

Spiller, etal. Palliative Medicine, 2006; 20: 17-23






Mixed Sedate




Delirium: Presentation Terminal


Cardinal sign of imminent death (hours-days)

86% Imminently Dying

Hypoactive >80%

Refractory to correction in some cases (50%)

Spiller, etal. Palliative Medicine, 2006; 20: 17-23

Delirium: Agitation Presentation



Picking Skin

Refusals of care

Vivid hallucinations




Spiller, JA. Pall Med 2006; 20: 17-23

Delirium: Family Experience

Impedes Communication Limits patient/family precious time

Creates anxiety & fear

Overwhelm with care of patient Feel premature separation Shift in burden of decision-making

Delirium: Guiding Steps for Family

and Clinician

Normal in advanced disease Treatable in most Patients and familys goals of care direct

evaluation, treatment Weigh burden of evaluation Evaluate likelihood a reversible etiology will be

found (50%) Feasibility of treatment

Delirium: Diagnosis (CAM)

Confusion Assessment Method

Inouye SK, etal. Ann Intern Med;113:941-948

Acute Onset & Fluctuating Course

AND Inattention

+ either


Thinking Altered LOC

Delirium: Evaluation

Caregiver interview: Is Mrs. X more confused lately?

Confusion Assessment Method (CAM)

Head to toe exam

Medication, substance use Review (Tox screen)

Infection (LP, Cultures, CXR)

Metabolic (CMP, CBC, ABG, TSH, Folate, B12, RPR, HIV)

Underlying Palliative Dx (MRI, CT, EEG, EKG, ECHO)

Delirium: Differential Diagnosis

Delirium: 1st Line Prevention


Frequent Reorientation

Familiar setting, caregivers

Oral Rehydration

Attention to Lighting

Sensory Aides

Avoid Restraints/immobilization

Daily Routine: Limit under/over stimulation

Sleep Routine

Delirium: 1st Line Management

Treatment of underlying cause

Multi-factorial, GOC directed

Medications Review

High risk: Steroids, Opioids, Anti-cholinergic, Antibiotics

Rotate opioids

Wean benzodiazepines and anticholinergics

Treat withdrawal, intoxication

Delirium: 1st Line Management

Supportive care:

Nutrition: assistance, supplements, PPN

Pain: schedule analgesics

Skin: oral and body hygiene, change position

Bowels: schedule softner, laxative

Delirium: 1st Line Management

Family/Caregiver Education

Reversible 50-80% cases, 1 week

Longer course severe illness

Representation of active dying

Non-pharmacolgic interventions

Role of medications to treat Agitation:

Neuroleptics, Sedatives

Drug category Indication Examples Benefit/SE

Antipsychotics Dopamine 2 receptor

1st line agitation

Haloperidol 0.5-2 mg po, IV q 30. T 4h. Max 5 mg/24 hr Chloropromazine 12.5-25 mg q 30 min, max 100mg/24. T 16h. Olanzapine 2.5-5 mg po qd, max 20 mg. T 20 h. Quetiapine 12.5-25 bid, max 400/d T 6h.

Also helpful nausea, hiccups (SE) sedation, falls, dry mouth, EPS, hypotension

Risk death RR 1.7 cerebrovascular, cardiac events elderly Less EPS risk atypicals; quetiapine most sedating

Benzodiazepines GABA-A receptor

2nd Line Added agent for Agitation 1st Line if Etoh or BZD withdrawal etiology

Lorazepam po, IV 0.5-5 mg bolus q 4 hour. T Midazolam iv, sc 0.5-5 mg bolus, 0.5-10 mg/hr infuse

Treat seizures and myoclonus (SE) sedation, confusion, paradox agitation, falls Midazolam short T1/2

Sedatives GABA-A receptor

Refractory Agitation Propofol IV 2.5-5 mcg/kg/min (titrate q 10 min)