Transcript S15_Delirium

Seminar in Palliative Care
September 26 – October 02, 2010
Salzburg, Austria
in Collaboration with
The
EPEC-O
TM
Education in Palliative and End-of-life Care - Oncology
Project
The EPEC-O Curriculum is produced by the EPECTM Project with major funding
provided by NCI, with supplemental funding provided by the Lance Armstrong
Foundation.
Delirium
Frank D. Ferris, MD, FAAHPM
Institute for Palliative Medicine
at San Diego Hospice
University of California San Diego
University of Toronto
The Butcher, Baker, and Candlestick Maker
Return: Interdisciplinary Goal-Based
Approaches to Delirium
Recognition, Work-Up, and Management
Scott A. Irwin, MD, PhD
Director, Psychiatry Programs
Rosene D. Pirrello, RPh
Director, Pharmacy
Jeremy M. Hirst, MD
Assistant Director, Psychiatry
Gary T. Buckholz, MD
Director, Fellowship Program
Frank D. ferris, MD, FAAHPM
Director, International Programs
© 2010
Key Topics…
Definition
Prevalence &
consequences
Many causes
Assessment
 Common language
 History & exam
 Tools
Under recognition  Differential
diagnoses
 Goals of care
 Diagnostic workup
…Key Topics
Management
Non–pharmacological
Pharmacological
 Reversible
 Irreversible
 Terminal
Delirium Is...
Change in mental status, impaired
 Attention
 Orientation
 Cognition
 Consciousness
 Reality
 Behavior
American Psychiatric Association. (2000)
Diagnostic and statistical manual of mental disorders. 943
. . . Delirium Is
Develops quickly
May fluctuate
Underlying medical etiology
NOT dementia
American Psychiatric Association. (2000)
Diagnostic and statistical manual of mental disorders. 943.
Associated changes
 Day-night reversal
 Emotional states
 Non-specific neurological abnormalities
 Decline in functional ability
Types
 Hyperactive
 Associated behavioral disturbances
 Hallucinations
 Delusional beliefs
 Hypoactive
 Quiet
 Mistaken for depression or fatigue
 Mixed – waxing and waning
Delirium is Highly Prevalent
and has
Serious Consequences…
Reported Prevalence
Hospitalized elderly
14 – 56 %
ICU
70 – 87 %
Advanced cancer
and / or end-of-life
25 – 85 %
Consequences...
6 month mortality
up to 25 %
Increased mortality
10 – 78 %
Prolonged hospitalizations
…Consequences...
Stress, discomfort,
reduced quality of life
Patients, nurses, family members
Even if hypoactive
Namba M, et al. (2007) Palliat Med 21: 587
Morita T, et al. (2007) J Pain Symptom Manage 34: 579
Cohen, MZ, et al. (2009) J Palliat Care 25:164
Bruera, E, et al. (2009) Cancer 15:2004
…Consequences
101 cancer patients who recovered from
delirium, 54 % recalled experience
 Hypoactive delirium 43 %
 Hyperactive delirium 66 %
Distress ( many reported severe )
 Patients
3.2 out of 4
 Spouses / caregivers 3.75
 Nurses
3.09
Breitbart W, et al. (2002) Psychosomatics 43: 183
Video – Hypoactive Delirium
Key points
1. Pathophysiology
2. Assessment
3. Management
Delirium has
Many, Many Causes…
Many are Discoverable
and Reversible…
Medical Causes of Delirium
Levenson JL, (2005)
The American
Psychiatric Publishing
textbook of
psychosomatic
medicine
See Appendix in
Handout
Medications Causing Delirium
Levenson JL, (2005)
The American
Psychiatric Publishing
textbook of
psychosomatic
medicine
See Appendix in
Handout
Most Common Causes…
Fluid imbalance
Medications
Infections
 Anticholinergics
Hepatic / renal
failure
 Benzodiazepines
Hypoxia
 Opioids
 Steroids
Hematological disturbance
…Most Common Causes
Hazard ratio of developing delirium
( 43 inpatients with cancer )
Benzodiazepines
2.04 if > 2 mg / day ( 1.05 – 3.97 )
Corticosteroids
2.67 if > 15 mg / day ( 1.18 – 6.03 )
Morphine equivalents
2.12 if > 90 mg / day ( 1.09 – 4.13 )
Gaudreau JD, et al. (2005) J Clin Oncol 23: 6712
Many Causes are Treatable...
237 hospice inpatients with cancer
 213 ( 90 % ) had 245 episodes of
delirium
 Causes found in
93 of the 153 who had a workup
Multi-factorial in > 50 %
 Complete remission in 20 %
Morita T, et al. (2001) J Pain Symptom Manage 22: 997
…Many Causes are Treatable
104 inpatients with advanced cancer
receiving palliative care
 71 had 94 episodes of delirium
 Reversible in 50 %
Lawlor PG, et al. (2000) Arch Intern Med 160: 786
Delirium is
Under–Recognized…
Often Under–Recognized...
2716 hospice patients
Delirium recognized in only
17.8 % of home care patients
28.3 % of inpatients
Irwin SA, et al. (2008) Palliative and Supportive Care 6: 159
…Often Under–Recognized
107 end-stage cancer inpatients
Delirium recognition rate : 44.9 %
20.5 % of hypoactive cases
Fang CK, et al. (2008) Jpn J Clin Oncol 38: 56
Why Under–Recognized ?
Complex presentation
Inconsistent language
Hypoactive sub-type
Thought to be normal part
of end-of-life
Careful Assessment &
Communication of Findings
is Key to Successful
Management of Delirium…
Common Language
is Essential…
Assessment
 Clinical history, physical
examination, observations over time
 Mental status exam
 Review of medication use
 Thorough medical and laboratory
work-up to elucidate underlying
cause
History
Context of the patient
Symptoms
 Quality
 Severity
 Temporal profile
 Effect of treatments
Assessment Tools…
“ Gold Standard ”
 Experienced clinician
 DSM-IV criteria
Three types of standardized tools
1. Screening
2. Diagnosis
3. Symptom severity
Sensitivity 94 – 100 %
Specificity 90 – 95 %
Laurila JV, et al. (2002) Int J Geriatr Psychiatry 17: 1112
Inouye SK, et al. (1990) Ann Intern Med 113: 941
Differential Diagnoses
to Consider…
American Psychiatric Association. (2000)
Diagnostic and statistical manual of mental disorders. 943
Differentiate Delirium From
Dementia
Psychotic disorders
Depression
Personality disorders
Anxiety
Developmental disorders
Akathisia
Dementia
Slow decline in brain function
> expected with normal aging
May have
 Problems with memory, attention,
language, emotions, & problem solving
 Confusion, hallucinations, delusions
Delirium vs. Dementia
Delirium
Dementia
Yes
No
Onset
Hours to days
Gradual
Fluctuation
Often
No
Change in
alertness
Depression
Symptom, episode, recurrent disorder
Major depression
 Several symptoms
 > 2 weeks duration
 Impaired function
Delirium vs. Depression
Delirium
Depression
Yes
No
Onset
Hours to days
Gradual
Fluctuation
Often
No
Change in
alertness
Potential Reversibility
of Delirium
Guides Work-up &
Management…
Potential Reversibility of Delirium
Potentially Reversible
Irreversible
 Patient is dying ( terminal delirium )
 Goals of care
 Work–up / reversal unsuccessful
Goals of Care
Initial patient & family goals
 Goals can change
Goals after diagnosis
 Diagnostic work-up vs. palliate
Goals after work-up
 Reverse vs. palliate vs. irreversible
Diagnostic Work-up May Include
Chemistry
Cardiac
Hematology
Infection
Endocrine
Toxicology
Vitamin levels
Imaging
Delirium
Management…
Management Strategies…
Ensure safety
Address environment
Manage based on
potential reversibility & goals of care
Adapted from APA Practice Guidelines 2004
American Psychiatric Association. (1999) Am J Psychiatry 156: 1
Cook IA. (2004) Available online at:
http://wwwpsychorg/psych_pract/treatg/pg/prac_guidecfm
…Management Strategies…
Reverse
 Treat underlying causes
Relieve
 Non-pharmacological
 Pharmacological
Consult psychiatry
…Management Strategies
Treatment
Benefits
Risks
Burdens
Time-limited therapeutic trials
Always Use
Non-pharmacological
Treatments…
Non-Pharmacological
Treatments Can Address
Disordered
thinking
Risk of falls / injury
Disorientation
Dehydration
Sleep
disturbance
Environmental factors
Immobility
Sensory deprivation
Prevention of Delirium...
852 patients age > 70 admitted to medicine service
Target
Treatment
Orientation
Introduce care team / daily schedule
each shift, oriented 1 – 3x / day
Activity
Cognitive stimulation 3x / day
Mobility
Ambulate / range of motion 3x / day
Sleep
Non-pharmacological sleep protocol
Sensory aids
Glasses, hearing aids
Dehydration
Rehydrate as needed
…Prevention of Delirium
In the treatment group
 Fewer episodes of delirium
62 vs. 90 ( 9.9 % vs. 15 %, p = 0.03 )
 Shorter duration
105 vs. 161 days ( p = 0.02 )
Followup showed up to an
89 % reduction of risk of delirium
Inouye SK, et al. (1999) N Engl J Med 340: 669
Inouye SK, et al. (2003) Arch Intern Med 163: 958
Use Pharmacological
Treatments when
Appropriate…
& Appropriately…
Pharmacological Management
No medication is FDA approved for the
treatment of delirium
No published double-blind, randomized,
placebo controlled trials
No consensus among oncologists,
geriatricians, psychiatrists, or
palliative medicine specialists
Agar M, et al. (2008) Palliat Med 22: 633
Delirium Management Decision Tree
Context &
Reasonable Goals of Care
Potentially Reversible
Irreversible
Hyperactive
Hypoactive
Hyperactive Hypoactive
Medical Rx
Medical Rx
Medical Rx Medical Rx
Successful Unsuccessful
Potentially Reversible, Hyperactive
Context &
Reasonable Goals of Care
Potentially Reversible
Hyperactive
Reverse Cause
Antipsychotics
Antipsychotic Indications
Indication
Drug
Anti Muscle
Sedation Amnesia
agitation
relaxation
Anti convulsant
Haloperidol





Chlorpromazine





Risperidone





Olanzapine





Quetiapine





1st Line
Pharmacological Treatment
Double-blind RCT of 30 AIDS patients
Haloperidol 0.4 ‒ 3.6 mg daily, n = 11 vs
Chlorpromazine 10 ‒ 80 mg daily, n = 13 vs
Lorazepam 0.5 - 10 mg daily, n = 6
Haloperidol = chlorpromazine >> lorazepam
Haloperidol & chlorpromazine minimal side effects
Lorazepam stopped early due to adverse events
Breitbart W, et al. (1996) Am J Psychiatry 153: 231
PEARL
Use 1st generation antipsychotics
Do Not Use Benzodiazepines
 Not first-line treatment
 Increase confusion, disinhibition, falls
 Necessary for alcohol or sedative withdrawal
APA Practice Guidelines 2004
American Psychiatric Association. (1999) Am J Psychiatry 156: 1.
Cook IA. (2004) Available online at:
http://wwwpsychorg/psych_pract/treatg/pg/prac_guidecfm
Application of
Pharmacological Principles
Improves Management…
Plasma Concentration
Anti-psychotic
Pharmacokinetic Guidelines
Cmax
SC / IM  30 min
Cmax
PO / PR  60 min
t1/2  24 hrs
0
Half-life ( t1/2 )
Time
Sample Orders… For Agitation
Haloperidol – 1 mg SC q 30 min PRN
If 3 doses not effective, call MD
Do not exceed 100 mg in 24 hr
Schedule today’s PRNs tomorrow
1 or 2 x / day + same PRN schedule
Chlorpromazine – 50 mg SC q 30 min PRN
If 3 doses not effective, call MD
Do not exceed 2000 mg in 24 hr
Schedule today’s PRNs tomorrow
1 or 2 x / day + same PRN schedule
…Pharmacological Management
Haloperidol = Olanzapine & Risperidone
1. Haloperidol 1 - 28 mg daily, n = 45 vs
Olanzapine 2.5 - 13.5 mg daily, n = 28
2. Haloperidol 1.5 - 10 mg daily, n = 11vs
Olanzapine 5 - 15 mg daily, n = 11
3. Haloperidol
1 - 3 mg daily, n = 12 vs
Risperidone 0.5 - 2 mg daily, n = 12
PEARL
Treat agitation like a
breakthrough symptom, e.g., pain
Provide breakthrough ( PRN ) doses on the
Time to maximum concentration ( TCmax )
If 3 doses not effective, call MD
( time-limited trials )
Provide routine doses
once every Half-life ( t½ )
Management of
Severe Agitation…
When is Agitation an Emergency ?
Aggression to property,
hostile verbal behavior
Irritability, intimidation
Mood lability, loud speech
Motor restlessness,
purposeless movements
Uncooperative,
intense staring
Allen et al. Treatment of Behavioral Emergencies Expert Consensus, 2001
Hierarchy of Treatments
Seclusion and / or Restraint
Emergency Medication
Show of Force
Voluntary Medication
Verbal Intervention
Needs Check
e.g., food, water, pain, etc.
Severe Agitation...
If imminent risk of harm to self or others
Haloperidol 2 - 5 mg
+ Diphenhydramine* 50 - 100 mg x 1
( protects against EPS & adds sedation )
± Lorazepam 1 - 2 mg ( or Midazolam )
In same syringe, mix very slowly in order
Lorazepam  Haloperidol  Diphenhydramine
…Severe Agitation – Alternatives…
Chlorpromazine 50 - 100 mg SC
 Increase dose by 50 mg once every
Time to Maximum Concentration ( tCmax )
until controlled
 Up to 2 gm / day
 If SC administration painful, e.g., burning,
consider IV infusion with dexamethasone
 Likely don’t need diphenhydramine
 ± Lorazepam
…Severe Agitation - Alternatives
Olanzapine 5 - 10 mg IM
 May repeat x 1 in 2 hr
 May repeat x 1 again 4 hr later
 Up to 30 mg / day ( Expensive )
Ziprasidone 10 - 20 mg IM
 May repeat 10 mg every 2 hr
 May repeat 20 mg every 4 hr
 Up to 40 mg / day ( Expensive )
Antipsychotics – Black Box Warnings
Drug
Increased
Suicidal
Mortality in Ideation in
Warning
DementiaChildren,
related
Adolescents,
Psychosis Young adults
Post injection
Delirium
Sedation
Syndrome
Haloperidol



Chlorpromazine



Risperidone



Olanzapine



Quetiapine



Antipsychotics – Sudden Cardiac Death
Agent(s) 1st Generation
Dose in
Incidence-Rate
CPZ equiv
Ratio
Low
< 100 mg
Moderate
100–299 mg
High
> 300 mg
2nd Generation
Incidence-Rate
Ratio
1.31
1.59
2.01
2.13
2.42
2.86
P values significant for dose-response relationship
P value not significant for 1st vs. 2nd generation risk
NEJM 2009; 360 : 225 - 35
Potentially Reversible, Hypoactive
Context &
Reasonable Goals of Care
Potentially Reversible
Hypoactive
Reverse Cause
?
Delirium Management Decision Tree
Context &
Reasonable Goals of Care
Potentially Reversible
Irreversible
Hyperactive
Hypoactive
Hyperactive Hypoactive
Medical Rx
Medical Rx
Medical Rx Medical Rx
Successful Unsuccessful
Terminal Delirium
Delirium during dying process
Prospective, irreversible
Altered level of consciousness
Oliguria / anuria
Tachycardia
Cyanosis
Abnormal breathing patterns
Peripheral
cooling
Loss of swallow / gag
Oral / tracheal secretions
Loss of sphincter control
Venous pooling /
mottling
Two Roads to Death
Confused
Tremulous
Restless
DIFFICULT ROAD
( Hyperactive )
Hallucinations
Normal
Mumbling Delirium
Sleepy
Myoclonic Jerks
Lethargic
USUAL ROAD
( Hypoactive )
Seizures
Obtunded
Semicomatose
Comatose
Dead
Irreversible Terminal, Hyperactive
Signs of Active Dying
Irreversible
Hyperactive
Support
Benzodiazepines,
Barbiturates, Propofol
Benzodiazepine Indications
Indication
Drug
Anti Muscle
Sedation Amnesia
agitation
relaxation
Anti convulsant
Lorazepam





Midazolam





 /







Antipsychotics
Opioids

Sample Orders to Control Agitation…
Lorazepam PO / Buccal Mucosa
 Starting dose = 1 mg PO / Buccal q 1 h PRN
 If 3 doses not effective, call MD
 Up to 40 mg in 24 hr
 Schedule today’s PRNs tomorrow q 8 h +
PRN doses q 1 h
…Sample Orders to Control Agitation…
Midazolam SC
 Loading dose = 0.2 mg / kg
then 0.1 mg / kg q 30 min x 2 PRN
 Maintenance dose / hr =
25 % total dose to sedate
 Consider alternative if need > 10 mg / hr
…Sample Orders to Control Agitation…
Propofol IV
 Starting dose = 1 mg / kg / hr
 Increase by 0.5 mg / kg / hr increments
every 15 – 30 min PRN
 Maximum for EOL = 6 mg / kg / hr
…Sample Orders to Control Agitation
Phenobarbital IV or SC
 Loading dose = 10 mg / kg
 May repeat x 2 within 2 – 3 hrs
 Continuous infusion 10 – 20 mg / hr
 Titrate PRN
 Maintenance = 600 – 2400 mg / 24 hr
PEARL
Treat agitation like a
breakthrough symptom, e.g., pain
Provide breakthrough ( PRN ) doses on the
Time to maximum concentration ( TCmax )
If 3 doses not effective, call MD
( time-limited trials )
Provide routine doses
once every Half-life ( t½ )
Benzodiazepines
Lethal Doses
 Lorazepam LD 50
= 5,000 mg
 Midazolam LD 50
= 10,000 mg
Don’t worry about
 Amnesia, confusion, restlessness
 Hypotension
 Respiratory depression
Irreversible, Hyperactive
Goals of Care or
Work-up / Treatment Unsuccessful
Irreversible
Hyperactive
Support
Antipsychotics,
Benzodiazepines,
Barbiturates, Propofol
Irreversible, Hypoactive
Goals of Care or
Work-up / Treatment Unsuccessful
Irreversible
Hypoactive
Support
?
Mental Health Experts Can Help
Diagnoses often complex
Clinicians unfamiliar with
non-pharmacological treatments
Clinicians often uncomfortable with
pharmacological treatments,
especially off-label use
Develop new treatments
Key Topics…
Definition
Prevalence &
consequences
Many causes
Assessment
 Common language
 History & exam
 Tools
Under recognition  Differential
diagnoses
 Goals of care
 Diagnostic workup
…Key Topics
Management
Non–pharmacological
Pharmacological
 Reversible
 Irreversible
 Terminal
Summary
Cases can be complex
Clinicians often unfamiliar
with all possible treatments
Complex cases stressful