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NEW RESEARCH DIRECTIONS IN 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. Talks/U Penn IOA talk 2006_delirium research.ppt.

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New research directions in delirium l.jpg

NEW RESEARCH DIRECTIONS IN 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

Talks/U Penn IOA talk 2006_delirium research.ppt


What is delirium acute confusional state l.jpg
WHAT IS DELIRIUM?(Acute Confusional State)

Definition:

  • acute decline in attention and cognition

    Characteristics:

  • common problem

  • serious complications

  • often unrecognized

  • may be preventable


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WHAT WE WILL COVER:

  • Overview of delirium

  • Where we have come so far…

  • Where we are going…

  • What we still have to do…


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WHAT WE KNOW ABOUT DELIRIUM

  • Common problem

  • Often unrecognized

  • Typically of multifactorial etiology

  • Serious complications

  • Often preventable (40-50% cases)

    ------------------------------------------------------

    We will review each of these areas



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EPIDEMIOLOGY OF DELIRIUM

Delirium Rates

Hospital:

  • Prevalence (on admission) 10-40%

  • Incidence (in hospital) 15-60%

    Postoperative: 15-53%

    Intensive care unit: 70-87%

    Nursing home/post-acute care: 20-60%

    Mortality

    Hospital mortality: 22-76%

    One-year mortality: 35-40%


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CURRENT IMPACT OF DELIRIUM

  • 35% of the U.S. population aged ≥ 65 years is hospitalized each year, accounting for > 40% of all inpatient days

  • Assuming a delirium rate of 20%:

    • 7% of all persons ≥ 65 years will develop

      delirium annually

    • Delirium will complicate hospital stay for > 2.2 million persons/year, involving > 17.5 million

      in-patient days/year

  • Estimated costs: > $8 billion/year


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IMPACT OF DELIRIUM

Beyond hospital costs

Post-hospital costs (>$100 billion in 1 year)

  • Institutionalization

  • Rehabilitation

  • Home care

  • Caregiver burden

    Aging of U.S. population

    Ref: Leslie DL et al. Gerontologist 2005: 45 (Spec Iss II): 299.



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RECOGNITION OF DELIRIUM

  • Previous studies: 32-66% cases unrecognized by physicians

  • Yale-New Haven Hospital study (1988-1989):

    • 65% (15/23) unrecognized by physicians

    • 43% (10/23) unrecognized by nurses


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NURSES’ RECOGNITION OF DELIRIUM

  • Compared nurse recognition of delirium with interviewer ratings (N=797)

  • Nurses recognized delirium in only 31% of patients and 19% of observations

  • Nearly all disagreements in ratings were due to under-recognition by nurses

  • Risk factors for under-recognition: hypoactive delirium; advanced age, vision impairment, dementia

    Ref: Inouye SK, Arch Intern Med. 2001;161:2467-2473


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DEVELOPMENT OF THE CONFUSION ASSESSMENT METHOD (CAM)

Ref: Inouye SK, et. al. Ann Intern Med. 1990, 113: 941-8.


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SIMPLIFIED DIAGNOSTIC CRITERIA

-- Uses 4 criteria assessed by CAM:

(1) acute onset and fluctuating course

(2) inattention

(3) disorganized thinking

(4) altered level of consciousness

-- The diagnosis of delirium requires the presence of criteria:

(1), (2) and (3) or (4)


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VALIDATION OF CAM

Site ISite II

(n=30) (n=26)

Sensitivity 10/10 (100%) 15/16 (94%)

Specificity 19/20 (95%) 9/10 (90%)

Positive predictive

accuracy 10/11 (91%) 15/16 (94%)

Negative predictive

accuracy 19/19 (100%) 9/10 (90%)

Likelihood ratio

(positive test) 20.0 9.4


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CAM SIGNIFICANCE

  • Helped to improve recognition of delirium

  • Widely used standard tool for clinical and research purposes nationally and internationally

  • Translated into at least 8 languages

  • Used in over 200 original published studies to date


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I’ve seen a dying eye

Run round and round a room

In search of something, as it seemed,

Then cloudier become;

And then, obscure with fog,

And then be soldered down,

Without disclosing what it be,

‘Twere blessed to have seen.

Emily Dickinson



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MULTIFACTORIAL MODEL OF DELIRIUM IN OLDER PERSONS

Ref: Inouye SK et al. JAMA 1996; 275:852-857


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RISK FACTORS FROM PREVIOUS STUDIES

  • Reviewed medical literature for original articles which examined independent risk factors for delirium

  • Found 36 studies examining risk factors for delirium, summarized on next 2 slides


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PREDISPOSING OR VULNERABILITY FACTORS

Inouye SK. NEJM 2006;354:1157-65


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PRECIPITATING FACTORS OR INSULTS

Inouye SK. NEJM 2006;354:1157-65



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DELIRIUM OUTCOMES FROM PREVIOUS STUDIES

  • Reviewed medical literature for original articles which examined delirium-related outcomes

  • Found 34 studies, documenting that delirium is associated with poor outcomes (50% control for confounders):

    • Prolonged LOS

    • Nursing home placement

    • Death

    • Functional and/or cognitive decline



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THE YALE DELIRIUM PREVENTION TRIAL

Inouye SK. N Engl J Med 1999;340:669-76.


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YALE DELIRIUM PREVENTION PROGRAM

  • Designed to counteract iatrogenic influences leading to delirium in the hospital

  • Multicomponent intervention strategy targeted at 6 delirium risk factors

    Risk FactorIntervention

    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



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DELIRIUM PREVENTION TRIAL:SIGNIFICANCE

  • First demonstration of delirium as a preventable medical condition

  • Targeted multicomponent strategy works

  • Significant reduction in risk of delirium and total delirium days, without significant effect on delirium severity or recurrence

  • Primary prevention of delirium likely to be most effective treatment strategy

  • Effectiveness and cost-effectiveness of the program has been demonstrated in multiple studies.


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THE HOSPITAL ELDER LIFE PROGRAM(HELP)

A model of care to prevent delirium and functional decline in hospitalized older patients

Inouye SK, et al. J Am Geriatr Soc. 2000;48:1697-1706

Website: www.hospitalelderlifeprogram.org



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HELP WEBSITEhttp://hospitalelderlifeprogram.org

  • Educational materials: on acute hospital care and delirium in older persons for consumers, families, caregivers

  • Reference list: brief list by topic; comprehensive searchable bibliography

  • Weblinks: links to useful websites

  • HELP: general background information and study results


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OTHER DELIRIUM INTERVENTION TRIALS

  • Proactive geriatric consultation post hip fracture (Marcantonio, JAGS 2001): significant 36% risk reduction for delirium

  • Nursing education and consultation post hip fracture (Milisen, JAGS 2001): significant reduction in delirium duration and severity

  • Multifactorial interventions in medical patients (1-Lundstrom, JAGS 2005; 2-Naughton, JAGS 2005): 1-significant reduction in delirium duration and LOS; 2-significant reduction in delirium rate and hospital costs

  • Educational intervention for medical staff (Tabet, Age Aging 2005): significant reduction in delirium prevalence

  • Haloperidol prophylaxis (Kalisvaart, JAGS 2005): significant decreased severity and duration of postoperative delirium



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PATHOPHYSIOLOGY OF DELIRIUM

  • Poorly understood

  • Functional rather than structural lesion

  • Characteristic EEG findings (generalized slowing)

  • Final common pathway of many pathogenic mechanisms—resulting in a failure of cholinergic transmission



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AREAS FOR FUTURE RESEARCH

  • Is delirium completely reversible? Does it lead to permanent neurologic changes or dementia?

    • Some patients with delirium never recover

    • Increased rates of dementia following delirium

    • Neuronal injury from some contributors

    • Hypoperfusion by neuroimaging methods

  • Does delirium alter the trajectory of dementia?

    • Worse outcomes in dementia patients who develop delirium


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RELATIONSHIP OF DELIRIUM TO DEMENTIA

DeliriumDementia

A continuum of cognitive disorders


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DELIRIUM-SPECT STUDY (N=22)(Preliminary Study)

  • Perfusion results (standard comparisons):

    • Frontal lobe hypoperfusion in 5

    • Parietal lobe hypoperfusion in 6

    • Normal flow in 11

  • Paired scans (6): 3 with reversible defects in parietal lobes

    Ref: Fong T et al. J Geront Med Sci. 2006. In Press.


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IMPACT OF DELIRIUM ON AD TRAJECTORY

Slope BC-Slope AB = 2.7 points per year (N=34)

Zhang Y et al, 2006.


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NEW DIRECTIONS FOR RESEARCH

  • Long-term outcome studies of delirium

  • Cognitive reserve capacity: protective effect of education and activities on delirium

  • Biomarkers: identify disease and severity markers (dx and long-term sequelae)

  • Neuroimaging: identify long-term changes with sensitive methods (DTI, perfusion)

  • Genetic and molecular mechanisms


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MOLECULAR MECHANISMS LINKING DELIRIUM AND ALZHEIMER’S DISEASE

  • In neuronal cell culture, therapeutic levels of the inhalational anesthetic isoflurane results in A-beta generation and apoptosis

  • While anesthesia is identified as an important risk factor for postoperative delirium, its relationship to AD not well described.

  • Isoflurane contributes to mechanisms of AD neuropathogensis, and provides a plausible link between delirium and AD.

Xie Z. Anesthesiology 2006;104:988-94; Xie A. J Gerontol Med Sci 2006. In Press


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FUTURE RESEARCH DISEASE

Delirium may provide the unique opportunity for early intervention and prevention of cognitive damage



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DELIRIUM DISEASEHEALTH POLICY IMPLICATIONS

Delirium serves as a marker for quality of hospital care for the elderly

  • Often iatrogenic

  • Linked to processes of care

  • Common, bad outcomes

    Delirium serves as a window for identifying quality – improving changes.

    Inouye SK. Am J Med. 1999;106: 565-73


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ESTIMATING THE IMPACT OF DELIRIUM DISEASE

  • Fraction of a year of life lost (Leslie, AIM 2005)

  • >$100 billion in direct medical costs per year (Leslie, Gerontologist 2005)

  • National costs from preventable adverse events estimated at $17-29 billion per year

  • Delirium likely accounts for at least 1/4 to 1/3 of these costs, rivaling the amount spent on caring for people with HIV/AIDS.

  • Further studies to estimate the national impact of delirium will be key.


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HEALTH POLICY INITIATIVES DISEASE

  • CAM: In AHRQ’s National Quality Measures Clearinghouse (www.qualitymeasures.ahrq.gov)

  • Proposal for delirium as measure of hospital quality of care: hospital and quality organizations

  • Advocacy for delirium and delirium prevention programs (e.g., HELP): work with consumer and watchdog groups


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Add life to years, DISEASE

not years to life.


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“Knowing is not enough; DISEASE

we must apply.

Willing is not enough;

we must do.”

- Goethe


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