Confusion about Confusion: What the orthopedic surgeon needs to know about delirium

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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

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Delirium

• 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?

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Delirium

• What is it?

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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 resultfrom the drinking
  of a drug

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Synonyms Peer-reviewed literature

• Acute confusional state
• Acute mental status change
• Altered mental status
• Organic brain syndrome
• Toxic/metabolic encephalopathy

• Dysergastic reaction
• Subacute befuddlement

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Synonyms on the wards

• Agitated
• Confused
• Combative
• Crazy
• Lethargic
• Out of it

• Out to lunch
• Poor historian
• Seeing things
• Sleepy
• Uncooperative
• Wild man

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Take home point

• Recognizing and naming delirium is the first step
  in its appropriate management.

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Delirium

• How do you diagnose it?

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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

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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.

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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 7s, 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?

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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

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Delirium vs. Dementia

• Acute onset
• Inattention
• Sometimes abnl LOC
• Fluctuating minutes to hours
• Reversible

• Gradual onset
• Memory disturbance
• Normal LOC
• Fluctuating none or days to weeks
• Irreversible

Common Delirium superimposed on Dementia
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Take home point

• When in doubt, diagnose delirium!

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Delirium

• Why is it important?

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Common

• Orthopedic patients aged 70 and older
• 15-20 incidence after THR, TKR
• 25 incidence after laminectomy
• 50 incidence after hip fracture

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Morbid

• Hospital complications RR2-5
• Hospital death RR2-20!
• Increased nursing home placement RR3

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Delirium Central in a Cascade of Adverse Events
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Postop delirium complications
Outcome Delirium No Delirium Major
Complications 15 2 Before delirium
5 After delirium 10 Death
4 0.2
plt.001, unadjusted and adjusted
Marcantonio, et. al. JAMA. 1994, 271 134-139
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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 gt 60K

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Delirium

• What causes it?
• I. Basic pathophysiology

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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?

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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
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Delirium and Inflammatory Markers
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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

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Delirium and Neuron Injury Markers
Serum Tau Protein
Serum S-100ß
Ramlawi et. al., Ann Surg, 2006
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Summary Pathophysiology

• Multiple pathophysiologies
• Cholinergic failure
• Inflammation
• Different mechanisms may pertain in different
  clinical situations
• Some cases of delirium may cause direct neuronal
  injury

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Delirium

• What causes it?
• II. Epidemiological Model

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Risk Factors for Delirium

• Predisposing factors
• 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

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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

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Preoperative Prediction Rule

• Risk Factor Points
• Age 70 or older 1
• Cognitive impairment 1
• Severe physical impairment 1
• Alcohol Abuse 1
• Markedly abnl serum chemistries 1
• Aortic aneurysm surgery 2
• Non-cardiac thoracic surgery 1

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Performance of the Clinical Prediction Rule
Validation Set
Risk Points Incidence of Delirium Low
0 2 Medium 1, 2 11 High 3 or
more 50
Area under the ROC curve0.79
Marcantonio, et. al. JAMA. 1994, 271 134-139
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Postop (Precipitating) Factors for Delirium

• Low postoperative hematocrit (lt30)
• Meperidine (highly anticholinergic)
• Benzodiazepines
• high dose, long acting
• Pain at Rest

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Delirium

• What is appropriate workup?

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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

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Medication Review

• Include OTCs, PRNs, alcohol
• Recent changes, additions, discontinuations
• Biggest offenders
• sedative-hypnotics (esp. long, ultra short
  acting)
• opioid analgesics (esp. meperidine RR2.5)
• anti-cholinergic drugs (anti-histamines, TCAs,
  esp. tertiary amines, misc. others)

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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

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Common reversible factors

• 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

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Correct all reversible factors

• Dont stop at one!

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Delirium

• Can it be prevented?

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Delirium and Hip Fracture

• Hip Fracture gt300,000 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

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Intervention

• 10 modules
• adequate CNS oxygen
• fluid/electrolyte
• pain management
• psychoactive meds
• bowel/bladder
• nutrition
• mobilization
• postop complications
• environment
• management delirium

• Geriatrics consultation
• proactive preop, or within 24 hrs postop
• daily visits targeted recommendations
• structured protocol

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Geriatrics consultation

• 61 pts seen preop, all 24 hrs postop
• 104 recs, 77 adherence (32-100)
• Recs made in gt2/3 pts (adh)
• transfuse to hematocrit gt 30 (79)
• d/c urinary catheter by POD 2 (89)
• d/c or adjust psychoactive meds (83)
• RTC acetaminophen for pain (72)

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Impact of Geriatrics Consultation
Marcantonio et. al. JAGS. 2001 49 516-522
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Implications

• Delirium is not inevitable
• It is preventable using a proactive,
  multifactorial approach
• Evolution Geriatrics-Orthopedics Co-management
  service
• Hip fracture
• High risk elective patients

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How do you manage the delirious patient?

• Dos and Donts

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Agitated Behavior

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Drug Treatment of Agitation

• What / Who are we treating?
• Reduce agitation but prolong cognitive symptoms
• Only 4 RCTs (largest N73)
• 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
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Immobility

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Malnutrition

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Bowel and Bladder Dysfunction

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Shift focus of care

• Support
• Not control

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Summary

• 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

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