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