UPDATE ON DELIRIUM RESEARCH

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UPDATE ON DELIRIUM RESEARCH Powered By Docstoc
					    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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       WHAT IS DELIRIUM?
         (Acute Confusional State)
Definition:
  • acute decline in attention and cognition


Characteristics:
  •   common problem
  •   serious complications
  •   often unrecognized
  •   may be preventable

                                               3
WHAT WE WILL COVER:
•   Overview of delirium
•   Where we have come so far…
•   Where we are going…
•   What we still have to do…




                                 4
    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

                                                         5
DELIRIUM IS COMMON



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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%

                                             7
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

                                                        8
   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.

                                                                            9
DELIRIUM IS OFTEN
 UNRECOGNIZED



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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


                                               11
 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.


                                          14
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)
                                                 15
      VALIDATION OF CAM
                        Site I        Site 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

                                                   16
       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

                                                17
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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  DELIRIUM IS
MULTIFACTORIAL



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MULTIFACTORIAL MODEL OF DELIRIUM
       IN OLDER PERSONS




                                                 20
  Ref: Inouye SK et al. JAMA 1996; 275:852-857
       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
Demographics                       Decreased Intake
  Older age                          Dehydration
  Male gender                        Malnutrition
Cognitive status                   Drugs
  Dementia                           Multiple psychoactive drugs
  Cognitive impairment               High number of drugs
  History of delirium                Alcohol abuse
  Depression                       Medical Comorbidity
Functional status                    High severity of illness
  Functional dependence              High level of comorbidity
  Immobility                         Chronic renal or hepatic disease
  Poor activity level                Previous stroke
  History of falls                   Neurologic disease
Sensory impairment                   Metabolic derangements
  Vision impairment                  Fracture or trauma
  Hearing impairment                 Terminal illness
                                     HIV infection

Inouye SK. NEJM 2006;354:1157-65
                                                                        22
 PRECIPITATING FACTORS OR INSULTS
Drugs                                               Intercurrent illnesses
     Sedative hypnotics                                  Infections
     Narcotics                                           Iatrogenic complications
     Anticholinergic drugs                               Severe acute illness
     Polypharmacy                                        Hypoxia
     Alcohol or drug withdrawal                          Shock
Primary neurological diseases                            Fever/hypothermia
     Stroke, particularly nondominant hemispheric        Anemia
     Intracranial bleed                                  Dehydration
     Meningitis/encephalitis                             Poor nutritional status
Environmental                                            Low serum albumin
    Intensive care unit admission                        Metabolic derangements (e.g., electrolytes,
   Physical restraint use                                glucose, acid-base)
   Bladder catheter use                             Surgery
   High number of procedures                             Orthopedic surgery
   Pain                                                  Cardiac surgery
   Emotional stress                                      Duration of cardiopulmonary bypass
Prolonged sleep deprivation                              Non-cardiac surgery

Inouye SK. NEJM 2006;354:1157-65
                                                                                                   23
 DELIRIUM HAS
   SERIOUS
COMPLICATIONS


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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

                                                      25
 DELIRIUM IS
PREVENTABLE



               26
THE YALE DELIRIUM PREVENTION
            TRIAL


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




                                            27
      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 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



                                                                                       28
      YALE DELIRIUM PREVENTION TRIAL
                                     RESULTS

Outcome                    Intervention   Usual Care Group   Matched OR
                              Group           (N=426)            (CI)
                             (N=426)                          or p-value


Incident delirium, n (%)    42 (9.9%)       64 (15.0 %)      .60 (.39-.92)
                                                                p= .02
Total delirium days            105              161             p=.02

No. delirium episodes          62               90              p=.03


Delirium severity score        3.9              3.5             p=.25
Recurrence rate            13 (31.0%)        17 (26.6%)         p=.62

                                                                             29
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.
                                                            30
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



                                                             31
HELP SITES ACROSS THE USA




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          HELP WEBSITE
        http://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
                                              33
     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
                                                         34
WHERE WE ARE
  GOING…



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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
                                          37
Flacker JM. J Gerontol Biol Sci 1999;54:B239-46   38
         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


                                                       39
  RELATIONSHIP OF DELIRIUM
        TO DEMENTIA



Delirium                                  Dementia


           A continuum of cognitive disorders



                                                 40
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.
                                                                 43
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
                                          44
  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
                                                                                   45
        FUTURE RESEARCH


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




                                           46
WHAT WE STILL NEED
     TO DO…



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        DELIRIUM
HEALTH 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
                                               49
  ESTIMATING THE IMPACT OF
          DELIRIUM
• 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.

                                                   50
HEALTH POLICY INITIATIVES
• 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,
 not years to life.



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“Knowing is not enough;
    we must apply.

 Willing is not enough;
      we must do.”

                    - Goethe



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