Transcript Overview of Delirium: State of the Field

U13: Cancer and Aging:
Interventions to Prevent Delirium
Sharon K. Inouye, M.D., M.P.H.
Professor of Medicine
Beth Israel Deaconess Medical Center
Harvard Medical School
Milton and Shirley F. Levy Family Chair
Director, Aging Brain Center
Hebrew SeniorLife
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DSM5 CRITERIA FOR DELIRIUM
• Disturbance in attention and awareness (reduced
orientation to the environment)
• Disturbance develops acutely and tends to fluctuate
• An additional disturbance in cognition, (e.g., memory
deficit, language, visuoperceptual)
• Not better explained by a preexisting dementia
• Not in face of severely reduced level of arousal or coma
• Evidence of an underlying organic etiology or multiple
etiologies
Used with permission. American Psychiatric Association, 2013
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Why is delirium important?
•Common problem
•Serious complications
•Often unrecognized
•Typically multifactorial etiology
•Up to 40% cases preventable
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In U.S. hospitals today
5 older patients become
delirious every minute
2.6 million older adults develop delirium each year
U.S. Dept HHS, AoA Report, Profile of Older Americans 2011
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Delirium is common
Delirium Rates
Hospital:
• Prevalence (on admission)
• Incidence (in hospital)
Postoperative:
Intensive care unit:
Nursing home/post-acute care:
Palliative care:
Mortality
Hospital mortality:
One-year mortality:
14-24%
6-56%
15-53%
70-87%
20-60%
up to 80%
22-76%
35-40%
Ref: Inouye SK, NEJM 2006;354:1157-65;
Lancet 2014; 383:911-922
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Delirium rates in cancer patients
Review of literature
• 10-50%: cancer patients undergoing surgery
(7 studies)
• 30-90%: advanced cancer patients receiving
palliative or terminal care (10 studies)
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Delirium has serious complications
• Delirium associated with:
– Increased morbidity and mortality
– Functional and cognitive decline
– Increased rates of dementia
– Institutionalization
– Increased LOS and healthcare costs
– Post-traumatic stress disorder
– Caregiver burden
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Delirium is expensive
Hospital costs (> $8 billion/year)
Post-hospital costs (>$150 billion/year)
• Rehospitalization
• Institutionalization
• Rehabilitation
• Home care
• Caregiver burden
Ref: Leslie DL, et al. Arch Intern Med 2008;168:27-32
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Causes in Cancer Patients
• Multifactorial
• Multimorbidity (multiple chronic conditions)
• Drugs
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–
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–
Chemotherapeutic agents
Steroids (Decadron)
Antiemetics (Compazine)
Anticholinergics (Benadryl)
Narcotics
Other psychoactive drugs (anxiety, depression, sleep)
• Infections (UTI, pneumonia)
• Metabolic derangements (↓Na, renal)
• Pain, sleep deprivation
Medications Associated with Delirium
[2012 AGS Beers Criteria: Potentially Inappropriate Medications for Elderly]
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All tricyclic antidepressants
Anticholinergics (eg, diphenhydramine)
Benzodiazepines
Corticosteroids
H2-receptor antagonists
Meperidine
Sedative hypnotics
Thioridazine/chlorpromazine
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Delirium is a preventable medical condition
• Previous studies documented at least 30-40%
of delirium is preventable
• Multiple successful strategies:
– Hospital Elder Life Program (Inouye 1999, 2000; Chen 2012)
– Proactive geriatric consultation (Marcantonio 2001)
– Exercise and rehabilitation interventions
(Caplan 2006, Schweickert 2009)
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NONPHARMACOLOGIC DELIRIUM PREVENTION:
HOSPITAL ELDER LIFE PROGRAM (HELP)
Considered gold standard of multicomponent interventions—included in AGS and NICE
guidelines
Targeted at 6 delirium risk factors
Risk Factor
Intervention
Cognitive Impairment………………………………….Reality orientation
Therapeutic activities protocol
Sleep Deprivation…………………………………….. Nonpharmacological sleep protocol
Sleep enhancement protocol
Immobilization………………………………………… Early mobilization protocol
Minimizing immobilizing equipment
Vision Impairment…………………………………….. Vision aids
Adaptive equipment
Hearing Impairment………………………………….. Amplifying devices
Adaptive equipment and techniques
Dehydration…………………………………………… Early recognition and volume repletion
Inouye SK. N Engl J Med 1999;340:669-76.
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HELP Impact on Outcomes
Reference
Rubin 2011
Chen 2011
Caplan 2007
Rubin 2006
Inouye 1999
Inouye 2000
Inouye 2000
Rubin 2011
Caplan 2007
Rubin 2006
Caplan 2007
Inouye 2009
Inouye 2009
Inouye 2009
Caplan 2007
Caplan 2007
No. of
Patients
Rate in HELP
Rate in Controls
Improvement
with HELP
PREVENTION OF DELIRIUM
>7,000
18%
41%
23%
179
0%
17%
17%
37
6%
38%
32%
704
26%
41%
15%
852
10%
15%
5%
REDUCED COGNITIVE DECLINE (MMSE decline by 2+ points)
1,507
8%
26%
18%
REDUCED FUNCTIONAL DECLINE (ADL decline by 2+ points)
1,507
14%
33%
19%
DECREASED HOSPITAL LENGTH OF STAY
>7,000
5.3 days
6.0 days
0.7 days
37
22.5 days
26.8 days
4.3 days
704
----0.3 days
REDUCED INSTITUTIONALIZATION
37
25%
48%
23%
DECREASED FALLS
-2%
4%
2%
-3.8/1000 p-y
11.4/.1000 p-y
7.6/1000 p-y
-1.2/1000 p-y
4.7/1000 p-y
3.5/1000 p-y
37
6%
19%
13%
DECREASED SITTER USE
37
330 hours
644 hours
314 hours
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HELP Impact on Costs
Reference
Rubin 2011
No. of
Patients
>7,000
Rizzo 2001
852
Leslie 2005
801
Caplan 2007
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Impact on Cost
>$7.3 million per year savings in hospital costs
(> $1000 savings per patient)
$831 cost savings per person-yrs in hospital costs
$9,446 savings per person-yrs in long-term
nursing home costs
$121,425 per year savings in sitter costs
•Many HELP studies have included oncology patients
•No studies have looked at oncology patients alone
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DELIRIUM MANAGEMENT:
NONPHARMACOLOGIC
Intervention
Results
Reference
Proactive geriatric
consultation
Decreased incidence of
delirium
Marcantonio
2001
Systematic detection
and specialized care
Trend towards cognitive
improvement
Cole 2002
Delirium Room
Reduced use of sedative
drugs
Flaherty 2003
Comprehensive
Geriatric Assessment
Reduced delirium severity
and duration
Pitkala 2006
Delirium Abatement
Program
Improved detection of
delirium by nurses in postacute setting
Marcantonio
2010
PHARMACOLOGIC APPROACHES
• Drug treatment may reduce agitation but
prolong delirium and cognitive decline
• Conclusion reached by several systematic
review and guideline panels:
No recommendation for drug treatment for
prevention or management of delirium at
this time
Ref: NICE 2010, VA HSRD 2011
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Gaps in our Knowledge
• Only 2 studies focusing strictly on cancer
patients only
• Gagnon P, 2012 [Psychooncology 2012;21: 187-94]
– Educational intervention for physicians and families
– Concurrent cohort design; N=1516 advanced CA
– Not effective for delirium prevention
• Hempenius L, 2013 [PLoS One 2013;8: e64834]
– Preoperative geriatric consultation with daily RN visit
– RCT; N=260 scheduled for elective surgery for CA
– Not effective for delirium prevention
• Interventions may have lacked potency
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Challenges: Nonpharmacologic studies
Studies can be challenging!!!
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Intervention of inadequate potency
Adherence with intervention not assured
Unblinded outcome assessment
Absence of control group
Lack of balanced allocation to study
groups
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Consider appropriate outcomes
• Review of ASCO’s 2014 Meaningful
Outcomes in Clinical Trials
• Oncology trials focus on survival
– PFS=progression free survival
• Patient-centered outcomes
– Health-related quality of life
– Delirium/Cognition
– Physical functioning
– Social and role functioning
– Sxs: Fatigue, nausea, weight loss, depression
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How to define “effectiveness”?
• Choose your endpoints carefully
• Delirium: [do not overweight agitation]
– Shortening duration and/or severity
– Decrease delirium recurrence
• Not delirium alone:
– Reduce adverse clinical outcomes (both
short- and long-term): mortality, LOS, costs,
readmission, NH placement
– Return to functional independence
• NB: Large sample size may be needed
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Approaches to Address the Gaps
• Randomized clinical trials of
nonpharmacological preventive strategies
– Pros: a gold standard approach and yield
definitive answers about effectiveness
– Cons: can be expensive, involving restrictive
populations, and often not completely real
world solutions
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Approaches (continued)
• Pragmatic trials of proven approaches, like
HELP
– Pros: can be applied in a real-world setting
– Cons: can also be expensive, since large
sample sizes needed to see effects
• Answers may be less definitive and may not be
considered gold standard
• Confounding factors may influence results strongly
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Approaches (continued)
• Quality improvement trials (before/after)
– Pros: can be useful for interventions where
effectiveness and cost-effectiveness already
well-established like HELP. Convincing local
evidence. Inexpensive, rapid turnaround.
– Cons: would not be considered a gold
standard approach
• Results may not be generalizable to other settings
or populations
• Historical studies susceptible to temporal trends,
confounding, and co-interventions
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Add life to years,
not years to life.
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