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Confusion about Confusion:
What the orthopedic surgeon
needs to know about delirium
Edward R. Marcantonio, M.D., S.M.
Orthopedic Surgery Grand Rounds
University of Massachusetts Medical School
November 12, 2008
Delirium
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What is it?
How do you diagnose it?
Why is it important?
What causes it?
What is the appropriate workup?
Can it be prevented?
How do you manage the delirious patient?
Delirium
What is it?
Delirium: early descriptions
• Celsus, 1st Century
“Sick people, sometimes in a febrile
paroxysm, lose their judgment and talk
incoherently… when the violence of the fit
is abated, the judgment presently returns…
• Aurelius, 2nd Century
“mental derangement may result…from the
drinking of a drug…”
Synonyms:
Peer-reviewed literature
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Acute confusional state
Acute mental status change
Altered mental status
Organic brain syndrome
Toxic/metabolic
encephalopathy
• Dysergastic
reaction
• Subacute
befuddlement
Synonyms: on the wards
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Agitated
Confused
Combative
Crazy
Lethargic
Out of it
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Out to lunch
Poor historian
Seeing things
Sleepy
Uncooperative
Wild man
Take home point:
Recognizing and naming delirium is the
first step in its appropriate management.
Delirium
How do you diagnose it?
DSM Definition
• First described in DSM-III, 1980
• Changes every few years
• DSM-IV:
– disturbance of consciousness with inattention
– develops over a short time and fluctuates
– change in cognition not explained by dementia
– Etiology: General Medical vs. Drug
Confusion Assessment Method
(CAM)
• Feature 1: Acute change in mental status
with a fluctuating course
• Feature 2: Inattention
• Feature 3: Disorganized thinking
• Feature 4: Altered level of consciousness
• Diagnosis of Delirium: requires presence
of Features 1 and 2 and either 3 or 4.
Testing Attention
• One of the most basic, but neglected
areas of the mental status exam
• Affects all other areas of cognition
• Formal methods:
– MMSE: Serial 7’s, WORLD backwards
– Digit Span: 5 forwards, 4 backwards
– Days of Week, Months of Year backwards
• Informal methods:
– LOC: Are the lights on?
– Attention: Is anybody home?
Psychomotor variants
• Hyperactive (“Wild man”): 25%
– most often recognized
– risk: oversedation, restraints
• Hypoactive (“Out of it”): 50%
– risk: failure to recognize
– sometimes confused with depression
• Mixed delirium: hypo alt with hyper
Delirium
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vs.
Acute onset
Inattention
Sometimes abnl LOC
Fluctuating: minutes
to hours
• Reversible
Dementia
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Gradual onset
Memory disturbance
Normal LOC
Fluctuating: none or
days to weeks
• Irreversible
Common: Delirium superimposed on Dementia
Take home point
When in doubt, diagnose
delirium!
Delirium
Why is it important?
Common
Orthopedic patients aged 70 and older
– 15-20% incidence after THR, TKR
– 25% incidence after laminectomy
– 50% incidence after hip fracture
Morbid
• Hospital complications: RR=2-5
• Hospital death: RR=2-20!
• Increased nursing home placement
RR=3
Delirium: Central in a Cascade of Adverse Events
Postop delirium: complications
Outcome
Major Complications
Before delirium
After delirium
Death
Delirium No Delirium
15%
2%*
5%
10%
4%
0.2%*
*p<.001, unadjusted and adjusted
Marcantonio, et. al. JAMA. 1994, 271: 134-139
Costly
• Acute hospitalization:
– increased LOS: 2-5 days
– increased inpatient costs
– common reason for “falling off” pathways
• Long term:
– increased short and long term NH placement
– incremental cost per pt over next year: > $60K
Delirium
What causes it?
I. Basic pathophysiology
Cholinergic failure hypothesis
• Acetylcholine: impt in cognitive processes
• Delirium:
– “caused” by anticholinergic poisoning
– reversed by pro-cholinergic drugs
– assoc. with “anticholinergic burden”
• Pilot RCT of donepezil in hip fx pts
– Cholinergic agonist used for dementia
– Can it prevent/treat delirium?
Inflammation and Delirium
• Delirium: inflammatory states
– Infections, cancer
• Delirium: common in cytokine treatment
• Inflammation:
– Breakdown of BBB
– Adversely impacts cholinergic transmission
• Several studies show assoc. between
delirium and inflammatory biomarkers in
medical and surgical patients
de Rooij et. al., J Psychosom Med, 2007
Delirium and Inflammatory Markers
Inflammatory
Marker
Delirium
(N=13)
No Delirium
(N=30)
P Value
C-reactive Protein
6 hrs postop
38 ± 11
17 ± 4
0.04
2.4 ± 0.3
1.2 ± 0.2
0.002
Interleukin-1β
6 hrs postop
Neuronal Injury Markers
• Measure neuronal damage in serum
• Examples:
– Neuron specific enolase
– S100 Beta
– Neuronal tau protein
• Delirium associated with release of
neuronal injury markers
Delirium and Neuron Injury
Markers
Serum Tau Protein
Ramlawi et. al., Ann Surg, 2006
Serum S-100β
Summary: Pathophysiology
• Multiple pathophysiologies:
– Cholinergic failure
– Inflammation
– Different mechanisms may pertain in
different clinical situations
• Some cases of delirium may cause
direct neuronal injury
Delirium
What causes it?
II. Epidemiological Model
Risk Factors for Delirium
• Predisposing factors:
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advanced age
pre-existing dementia
other CNS diseases
functional impairment
multiple comorbidities
multiple medications
imp. vision/hearing
• Precipitating factors:
– new psychoactive med
– acute medical problem
– exacerbation of chronic
medical problem
– surgery
– pain
– ?environmental change
Implications of Model
• More baseline vulnerability, less acute
precipitants needed
• Acute precipitants rarely in the CNS
• “Law of Parsimony” rarely applies:
– effective treatment requires evaluation and
correction of all reversible factors
Preoperative Prediction Rule
Risk Factor:
Age 70 or older
Cognitive impairment
Severe physical impairment
Alcohol Abuse
Markedly abnl serum chemistries
Aortic aneurysm surgery
Non-cardiac thoracic surgery
Points
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Performance of the
Clinical Prediction Rule: Validation Set
Risk
Low
Points
0
Incidence of Delirium
2%
Medium
1, 2
11%
High
3 or more
50%
Area under the ROC curve=0.79
Marcantonio, et. al. JAMA. 1994, 271: 134-139
Postop (Precipitating) Factors
for Delirium
• Low postoperative hematocrit (<30%)
• Meperidine (highly anticholinergic)
• Benzodiazepines
– high dose, long acting
• Pain at Rest
Delirium
What is appropriate workup?
Workup
• History:
– time course of mental status changes
– association with other “events”
• Physical examination:
– Vital signs: HR, BP, temp, oxygen sat.
– General medical: cardiac, pulmonary
– Neuro: new focal signs
Medication Review
• Include OTCs, PRNs, alcohol
• Recent changes, additions, discontinuations
• Biggest offenders:
– sedative-hypnotics (esp. long, ultra short acting)
– opioid analgesics (esp. meperidine: RR=2.5)
– anti-cholinergic drugs (anti-histamines, TCAs,
esp. tertiary amines, misc. others)
Laboratory testing
• CBC (hct, wbc), electrolytes, glucose
• Infectious workup: U/A, CXR, etc.
• Selected additional testing:
– drug levels, toxic screen, ABG, EKG
• ?role for CT/LP/EEG:
– new focal sxs, high suspicion, no other dx
Common reversible factors
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DRUGS
E lectrolyte imbalance (dehydration)
L ack of drugs (withdrawal, uncontr. pain)
I nfection
R educed sensory input (vision, hearing)
I ntracranial (CVA, subdural, etc.--rare)
U rinary retention/fecal impaction
M yocardial/Pulmonary
Correct all reversible factors
Don’t stop at one!
Delirium
Can it be prevented?
Delirium and Hip Fracture
Hip Fracture: >300,000 annually in U.S.
• Paradigm for acute functional decline in
hospitalized elderly
– Hip is easily fixed, but less than 50% recover
to pre-fracture status
• Delirium: affects 50% of hipfx pts
– Indpt risk factor for poor functional recovery,
even after adjusting for dementia
Intervention
• Geriatrics
consultation:
– proactive: preop, or
within 24 hrs postop
– daily visits: targeted
recommendations
– structured protocol
• 10 modules
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adequate CNS oxygen
fluid/electrolyte
pain management
psychoactive meds
bowel/bladder
nutrition
mobilization
postop complications
environment
management delirium
Geriatrics consultation
• 61% pts seen preop, all 24 hrs postop
• 10+4 recs, 77% adherence (32%-100%)
• Recs made in >2/3 pts (%adh):
– transfuse to hematocrit > 30% (79%)
– d/c urinary catheter by POD 2 (89%)
– d/c or adjust psychoactive meds (83%)
– RTC acetaminophen for pain (72%)
Impact of Geriatrics Consultation
Outcome
Geri
Consult
Usual
Care
P
value
Delirium
32%
50%
.04
Severe delirium
12%
29%
.02
2.9 days
3.1 days
.72
Days delirium
per episode
Marcantonio et. al. JAGS. 2001; 49: 516-522
Implications
• Delirium is not inevitable:
– It is preventable using a proactive,
multifactorial approach
• Evolution: Geriatrics-Orthopedics Comanagement service
– Hip fracture
– High risk elective patients
How do you manage
the delirious patient?
Do’s and Don’ts
Agitated Behavior
Drug Treatment of Agitation
• What / Who are we treating?
– Reduce agitation but prolong cognitive
symptoms
• Only 4 RCTs (largest N=73):
– Neuroleptics preferable to benzodiazepines
in most cases (excpt: PD, DLBD, ETOH)
– Low dose high potency neuroleptics (e.g.,
starting at haloperidol 0.25-1 mg)
– Newer “atypical” agents: no better than
haloperidol
Lacasse et. al., Ann Pharm, 2006
Immobility
Malnutrition
Bowel and Bladder
Dysfunction
Shift focus of care
Support
Not control
Summary
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Delirium: call it by its name
Diagnosis: Confusion Assessment Method
Important: Common, Morbid, Costly
Multiple pathophysiologies: no magic bullet
Assess and treat all correctable factors
Prevent delirium using a proactive approach
Support and rehabilitate the delirious patient