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 SchoolNovember 12, 2008
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?
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
• Acute confusional state• Acute mental status change• Altered mental status• Organic brain syndrome• Toxic/metabolic
encephalopathy
• Dysergastic reaction
• Subacute befuddlement
Synonyms: on the wards
• Agitated• Confused• Combative• Crazy• Lethargic• Out of it
• 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 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
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
*p<.001, unadjusted and adjusted
Marcantonio, et. al. JAMA. 1994, 271: 134-139
Outcome Delirium No DeliriumMajor Complications 15% 2%*
Before delirium 5% After delirium 10%
Death 4% 0.2%*
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
Interleukin-1β
6 hrs postop
2.4 ± 0.3 1.2 ± 0.2 0.002
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 Serum S-100β
Ramlawi et. al., Ann Surg, 2006
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:– 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: 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
Performance of the Clinical Prediction Rule: Validation Set
Area under the ROC curve=0.79
Marcantonio, et. al. JAMA. 1994, 271: 134-139
Risk Points Incidence of DeliriumLow 0 2%
Medium 1, 2 11%
High 3 or more 50%
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
• 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– 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
Days delirium per episode
2.9 days 3.1 days .72
Marcantonio et. al. JAGS. 2001; 49: 516-522
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
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
• 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