Section of Physical Medicine and Section of Physical Medicine and RehabilitationRehabilitation

presentspresents

GRAND ROUND GRAND ROUND 5/13/20055/13/2005

bybyAnthony Tam Pham, DOAnthony Tam Pham, DO

Case Report Ms. A, a 74-year old white woman who was

diagnosed w late-onset bipolar affective disorder at the age of 69, came to the hospital after sustaining a R hip fracture from fall. In the emergency room, she was alert and fully oriented. She received 4 mg of IV morphine sulfate for pain. She slept well and answered questions appropriately the next morning but was drowsy.

After hip arthroplasty the following day, she was awake but verbally unresponsive. The next day, she continued to exhibit a blank expression, lethargy, and minimal verbal responses.

Rehab was consulted for 9G placement for post-op rehab.

At the consultation, she displayed a fluctuating level of consciousness, was disoriented to place and time, had poor attention, uttered only a few words and short phrases, but was pleasant. She did not report feeling depressed, manic, or anxious. Her score on the Mini Mental State Examination was 10 out of 30. Her performance on the clock-drawing task was poor.

PMH: HTN, DM, bipolar disorder, CHF

no history of stroke, dementiaPSH: just hip arthroplastyAll: noneMed: Lopressor, Glucotrol, lithium, ASA,

Lovenox, Percocet prn, dulcolax.

Her psychiatrist recommended obtaining an EEG and Head CT. Results showed diffuse slowing and mild small vessel ischemic changes, respectively. EEG findings supported the diagnosis of delirium, and Ms A was given donepezil, 5 mg/day.

The next day, she was better but still confused and sleepy.

The second day, she was alert and conversant, and displayed some insight.

The following day, she was alert, fully oriented, displayed good eye contact and normal psychomotor activity. MMSE was 20/30.

She was then transferred to 9G for post-op rehab.

DELIRIUM:DELIRIUM:pathogenesis, diagnosis, and pathogenesis, diagnosis, and

treatmenttreatment

Definition and terminologyDefinition and terminology

DSM –IV1. Disturbance of consciousness with reduced

ability to focus, sustain, or shift attention.2. not better accounted for by a preexisting,

established, or evolving dementia.3. Over a short period of time (usually hours to

days), fluctuating during the course of the day4. Evidence that it is caused by a medical

condition, substance intoxication, or medication side effect.

Additional featuresAdditional features

Psychomotor behavioral disturbances such as hypoactivity, hyperactivity w increased sympathetic activity, impairment in sleep duration and architecture

Variable emotional disturbances, such as fear, depression, euphoria, or perplexity.

Epidemiology of deliriumEpidemiology of delirium

30% - older medical patients10-50% - older surgical patients70% - ICU42% - Hospice units16% - postacute care settingsDelirium patients experience prolonged

hospitalizations, functional decline, high risk for institutionalization.

Pathogenesis of deliriumPathogenesis of delirium

Poorly understoodDifficult to study severely ill patients Hard to separate from that of underlying

illness and drug treatment

Pathogenesis: 1.Neurobiology Pathogenesis: 1.Neurobiology of attentionof attention

Arousal and attention are governed by: the ascending reticular activating systemThe “nondominant” parietal and frontal

lobesIntact higher order integrated cortical

function

Pathogenesis: Pathogenesis: 2. Neurotransmitter2. Neurotransmitter

1. AcetylcholineCause delirium when given to healthy

personMore likely to lead to confusion in frailty

elderlyEffects reversed with cholinesterase

inhibitors (physostigmine).

Medical conditions precipitating delirium, such as hypoxia, hypoglycemia, thiamine deficiency, decrease acetylcholine synthesis in CNS

Alzheimer’s disease, characterized by a loss of cholinergic neurons, increases risk of delirium due to anticholinergic medications.

neurotransmittersneurotransmitters

2. Alterations in neuropeptides (eg, somatostatin), endorphins, serotonin, norepinephrine, and GABA

3. Cytokines, such as interleukins and interferons

Pathogenesis: (3) Pathogenesis: (3) risk factorsrisk factors

MultifactorialUnderlying brain diseases, such as

dementia, stroke, Parkinson’s diseaseAdvanced age and sensory impairment

Pathogenesis: (4) Pathogenesis: (4) precipitating factorsprecipitating factors

Polypharmacy (particularly psychoactive drugs)

InfectionsDehydrationImmobility (including restraint use)MalnutritionThe use of bladder catheters

Clinical presentation of Clinical presentation of deliriumdelirium

1. Disturbance of consciousness A change in the level of awareness and the

ability to focus, sustain, or shift attention.– Often subtle, may precede by one day or

more.– Patient “isn’t acting quite right”

Distractibility, often evident in conversation.

Appearing drowsy, lethargic, or even semi-comatose in advanced cases.

2. Change in cognitionCognitive problems: memory loss,

disorientation, difficulty with language and speech.– Need to ascertain baseline.

Perceptual problems: misidentify the clinician, vague delusions of harm.– Visual and tactile hallucinations are uncommon

3. Temporal courseDevelop over hours to days and typically

persist for days to monthsAcuteness of presentation is the most

helpful feature in differentiating from dementia.

Fluctuating: typically most severe in the evening and at night, and relatively lucid during morning.

4. Other featuresNot essential diagnostic but common,

including psychomotor agitation, sleep-wake reversals, irritability, anxiety, emotional lability, and hypersensitivity to lights and sounds.

Common among older patients includes relatively quiet, withdrawn state that frequently is mistaken for depression.

Evaluation of delirium (1)Evaluation of delirium (1)

Two important aspects to the diagnostic evaluation: recognizing that the disorder is present, and uncovering the underlying cause.

In some reports, clinicians fail to recognize delirium in 70 percent of cases.

Wrongly attributed to the patient’s age, to dementia, or to other mental disorders such as depression.

Must not “normalize” lethargy or somnolence by assuming that illness, sleep loss, fatigue, or anxiety cause the change.

Require knowledge of the patient’s baseline level of functioning.

Evaluation (2): Evaluation (2):

Confusion Confusion Assessment Assessment Method Method (CAM):(CAM):

- sensitivity of 94 - sensitivity of 94 to 100 percent;to 100 percent;- specificity of 90 - specificity of 90 to 95 percentto 95 percent- a standard - a standard screening device screening device in clinical studies in clinical studies of deliriumof delirium

Evaluation (3)Evaluation (3)

Investigating medical etiologies:– Fluid and electrolyte disturbances (dehydration,

hyponatremia and hypernatremia)– Infections (urinary, respiratory, skin and soft

tissue)– Drug or alcohol toxicity– Withdrawal from alcohol

– Withdrawal from barbiturates, benzodiazepines, and SSRI

– Metabolic disorders (hypoglycemia, hypercalcemia, uremia, liver failure, thyrotoxicosis)

– Low perfusion states (shock, heart failure)– Postoperative states, especially in the elderly

Evaluation Evaluation (4): (4):

medication medication reviewreview

Differential DiagnosisDifferential Diagnosis

1. Sundowning: a frequently seen but poorly understood; seen in evening hours; typically in demented, institutionalized patients.

2. Focal syndromes Temporal-parietal: patients w Wernicke’s

aphasia – not comprehend, obey, seem confused; but restricted to language.

– Occipital: Anton’s syndrome of cortical blindness and confabulation

– Frontal: bifrontal lesions (eg, from tumor or trauma) often show akinetic mutism, lack of spontaneity, lack of judgment, problems w recent or working memory, blunted or labile emotional responses.

3. Nonconvulsive Status Epilepticus (NCSE):– Requires EEG for detection– Show no classical ictal features– Features: prominent bilateral facial twitching,

unexplained nystagmoid eye movements during obtunded periods, spontaneous hippus, prolonged “ post-ictal state”, automatisms (lip smacking, chewing, swallowing movements).

4. Dementia– Alzheimer’s – cognitive change is insidious,

progressive, without much fluctuation, over a much longer time (months to years).

– Lewy bodies – similar to Alzheimer’s, but fluctuations and visual hallucinations are more common and prominent.

5. Primary psychiatric illnesses: – Depression (poor sleep, difficulty w attention or

concentration)– Mania

Laboratory testingLaboratory testing Serum electrolytes, creatinine, glucose, calcium,

CBC, and urinalysis Drug levels, when appropriate.

– Delirium can occur even w “therapeutic” levels (digoxin, lithium, or quinidine)

Toxic screen of blood and urine Blood gas: Respiratory alkalosis is due to early

sepsis, hepatic failure, early salicylate intoxication. Metabolic acidosis reflects uremia, diabetic ketoacidosis, lactic acidosis, late phases of sepsis or salicylate intoxication, methanol, ethylene glycol

NeuroimagingNeuroimagingHead CT may be used selectively rather

than routinely for evaluating delirium.May not be necessary if:

– An obvious treatable medical illness or problem– No evidence of trauma– No new focal neurologic signs are present– Patient is arousable and able to follow simple

commands.

Head CT may be required if: – Delirium does not improve despite appropriate

treatment of underlying medical condition– The neurologic examination is confounded by

diminished patient responsiveness or cooperation.

Lumbar punctureLumbar puncture

CSF analysis is the only diagnostic tool for the following mostly treatable conditions in delirium patients:– Bacterial meningitis– Encephalitis– Nonbacterial CSF pleocytosis (eg, aseptic

meningitis, carcinomatous meningitis, encephalitis, seizures)

– Elevated CSF glutamine concentration in hepatic encephalopathy

– Elevated opening pressure due to increased ICP

LP is mandatory when the cause of delirium is not obvious.

EEGEEG

Should be obtained for any patient with altered consciousness of unknown etiology.

Useful to:– Exclude seizures, esp. nonconvulsive or

subclinical seizures– Confirm the diagnosis of certain metabolic

encephalopathies or infectious encephalopatides

Nonconvulsive seizures lack motor manifestations or convulsions, but may impair consciousness.

Nonconvulsive status epilepticus may cause continuous or fluctuating impairment of consciousness.

Metabolic encephalopathies may show diffuse bilateral slowing of background rhythm and high wave amplitude.

Viral encephalitis may show diffuse background slowing and occasional epileptiform activity.

TreatmentTreatment

1. Multicomponent intervention Standardized protocols to control six risk factors for

delirium: cognitive impairment; sleep deprivation; immobility; visual impairment; hearing impairment; and dehydration.

Of 852 hospitalized pts aged 70 or older; resulted in significant reduction in the number of delirium episodes vs usual care ( 62 vs. 90) and in the total number of days w delirium (105 vs 161)

Inouye, Bogardus, Charpentier. A Multicomponent intervention to prevent delirium. NEJM 1999.

Managing disruptive Managing disruptive behaviorsbehaviors

Physical restraints should be used only as a last resort since they frequently increase agitation and create additional morbidity.

Hospital environment, characterized by high ambient noise, poor lighting, lack of windows, frequent room changes, and restraint use, often contribute to worsening confusion.

Frequent reassurance, touch, and verbal orientation from familiar persons lessen disruptive behaviors.

Psychotropic medicationPsychotropic medication

A review by the Cochrane Collaborative found only one high-quality randomized trial, which compared haloperidol, chlorpromazine, and lorazepam in the treatment of delirium

Recommendation: low-dose haloperidol (0.5 to 1.0 mg PO, IV, or IM) be used to control agitation or psychotic symptoms.

Jackson, Lipman. Drug therapy for delirium in terminally ill patients. The Cochrane Library, issue 2, 2004.

Older patients are more likely to experience severe extrapyramidal effects w haloperidol (akathisia, potential fatal neuroleptic malignant syndrome)

The newer antipsychotic agents (risperidone, olanzapine) have fewer extrapyramidal side effects.

Benzodiazepine (lorazepam 0.5 to 1.0 mg) have a more rapid onset of action (5 min after parenteral), but they commonly worsen confusion and sedation. Drug of choice only in cases of sedative drug and alcohol withdrawal.

SummarySummary::

Delirium Delirium workup workup schemescheme

SummarySummary: :

Common Common causes of causes of DeliriumDelirium

Summary: Summary: common common

culprit culprit drugsdrugs