delirium paul borghesani md-phd assistant professor psychiatry and behavioral sciences paulrb@uw.edu

Delirium

Paul Borghesani MD-PhDAssistant Professor

Psychiatry and Behavioral Sciencespaulrb@uw.edu

Delirium:Defining delirium

“an acute mental disturbance characterized by confused thinking and disrupted attention usually accompanied by disordered speech

and hallucinations”

akaacute confusional state

acute brain failureencephalopathy

global cognitive impairmentHippocrates “phrenitis”

“the great imitator”

Delirium:A gestalt

EtiologyCognitivedysfunctio

nPathophysiology

?Neuronal levelSystems level

Goals for today

Review the epidemiology and importance of detecting delirium

Learn the key features and subtypes of delirium

Explore the pathophysiology of delirium

Learn how to evaluate and treat delirium

Learn to recognize co-morbid delirium in mental illness

Who could be delirious?

An agitated, combative patient who does not follow instructions

An obtunded, minimally interactive patient

An emotionally erratic patient who makes contradictory remarks and who staff cannot logically engage

A calm, confused patient who is suspicious and oppositional

Clinical case:31 y/o with confusion

A 31 y/o previously healthy male is brought in by his roommate secondary to acute change in mental status. The patient is confused and bewildered and appears anxious and agitated. He denies medical problems and states that he takes medications for anxiety but cannot explain any details. He reports nausea, headache, tremor and myoclonus. He has mildly elevated WBC but his labs and vitals are within normal limits.

Questions:1)What factors suggest this is delirium?2)What is a possible etiology?

Clinical case:31 y/o with confusion

A 31 y/o previously healthy male is brought in by his roommate secondary to acute change in mental status. The patient is confused and bewildered and appears anxious and agitated. He denies medical problems and states that he takes medications for anxiety but cannot explain any details. He reports nausea, headache, tremor and myoclonus. He has mildly elevated WBC but his labs and vitals are within normal limits.

Questions:1)What factors suggest this is delirium?2)What is a possible etiology?

Clinical keys of delirium

Abrupt onset

Fluctuating symptoms

Difficulty sustaining attention

Appear to have cognitive dysfunction

Clinical case:31 y/o with confusion

A 31 y/o previously healthy male is brought in by his roommate secondary to acute change in mental status. The patient is confused and bewildered and appears anxious and agitated. He denies medical problems and states that he takes medications for anxiety but cannot explain any details. He reports nausea, headache, tremor and myoclonus. He has mildly elevated WBC but his labs and vitals are within normal limits.

Questions:1)What factors suggest this is delirium?2)What is a possible etiology?

Perry and Wilborn. Annals of Clinical Psychiatry. 24(2) 155 (2012)

Clinical case:Serotonin syndrome (SS)

Can be caused by any antidepressant

Most cases are associated with polypharmacy

Typical symptoms include- mental status changes, tremor, myoclonus, hyperreflexia, GI

symptoms, diaphoresis, fever, inducible clonus

Most often confused with neuroleptic malignant syndrome

- SS is associated with GI symptoms, myoclonus, mild or no laboratory changes

- NMS is associated with more severe rigidity and laboratory changes (low Fe, dramatically elevated creatine kinase, elevated WBCs)

Epidemiology and diagnosis of delirium

Hall R et at. Best Pract & Research Clin Anaesth, 2012 Inouye, S.K. N Engl J Med, 2006.

Epidemiology of delirium:It’s common!

Common in the general population- 0.4% of all people

- 1.0% in individuals over 55 (over 10% in those > 85)

- 60% of nursing home residents

Common in the medical setting- 10-30% of elderly in the ER

- 20% of all medical admissions

- 4-53% among hip fracture patients

- 4-28% of elective surgery patients

- 13-72% of cardiac surgery patients

Consequences of delirium

Increased length of stay

Increased mortality and morbidity- Perhaps between 25-75%, as high as MI and sepsis

Prolonged cognitive difficulties

Institutionalization

DSM-5

Delirium:DSM-5 diagnostic criteria

A. A disturbance in attention and awareness

B. The disturbance develops over a short period of time, represents a change in function, and fluctuates

C. There is a disturbance in cognitionmemory, disorientation, language, visuospatial ability, or perception

D. A and C are not better explained by an established neurocognitive disorder

E. Evidence from the history, PE or laboratory findings that this represents another medical condition, substance intoxication or withdrawal, toxin exposure or due to multiple etiologies.

DSM-5

Delirium:DSM-5 specifiers

Specify etiology- Substance intoxication delirium

- Substance withdrawal delirium

- Medication-induced delirium

- Delirium due to another medical condition

- Delirium due to multiple etiologies

Specify characteristics- acute (hours to days) or persistent (weeks to months)

- hyperactive, hypoactive or mixed

Classification of delirium: Hyperactive subtype

Agitated, uncooperative and often combative

Psychotic and responding to internal stimuli

Loud and fast speech

Wandering, restless

Appear intoxicated

Classification of delirium:Hypoactive subtype

Somnolent, inattentive, and uninterested

Poor memory and cognitive abilities

Will be described as having lapses or variable behavior

Reduced amount and rate of speech

Often missed because they can be left alone

Classification of delirium:Mixed subtype

Combination of both

Hypoactive and mixed account for about 80% of all cases

DSM-5

Delirium:Other DSM-5 delirium syndromes

Other specified delirium- the full criteria for delirium are not met

- you choose to specify WHY the criteria are not met

- e.g., “attenuated delirium syndrome”

Unspecified delirium- the full criteria for delirium are not met

- you choose NOT to specify why the criteria are not med

- often appropriate in the ED when etiologies are unknown

Clinical case:44 y/o non-compliant patient

A 44 y/o male is sustained multiple injures after being hit by a car. Two days after surgical admission psychiatry is consulted secondary to his variable refusal of care and an attempted elopement. He is described as intermittently yelling, throwing food, and RISing. He is homeless, has known mental illness and a history of alcoholism. The surgical team is asking if he has capacity to refuse care. When you meet with him he is disoriented to time and circumstance and is often incomprehensible because of mumbling and tangentiality.

Questions:1)What suggests he is having visual hallucinations?2)What is a possible etiology of his delirium?

Clinical case:44 y/o non-compliant patient

A 44 y/o male is sustained multiple injures after being hit by a car. Three days after surgical admission psychiatry is consulted secondary to his variable refusal of care and an attempted elopement. He is described as intermittently yelling, throwing food, and RISing. He is homeless, has known mental illness and a history of alcoholism. The surgical team is asking if he has capacity to refuse care. When you meet with him he is disoriented to time and circumstance and is often incomprehensible because of mumbling and tangentiality.

Questions:1)What suggests he is having visual hallucinations?2)What is a possible etiology of his delirium? (Hint: he vitals are

unstable)

Clinical case:Delirium tremens

Onset 2-3 days after last drink

Peaks 4-5 days

Severe autonomic hyperactivity- fever, tachycardia, tachypnea, hypertension, tremor diaphoresis

Delirium- confusion, disorientation, agitation, perceptual disturbances including

visual hallucinations

- may/may not be accompanied by seizures

Treat with benzodiazepines

Must have Features 1 & 2 and either 3 or 4

The confusion assessment method (CAM):An alternative to the DSM-5

Feature 1: Acute onset or fluctuating course- usually obtained from an informant

Feature 2: Inattention- from your evaluation, are they distractible or unable to follow the

conversation

Feature 3: Disorganized thinking- rambling, confused, derailment, illogical, loose associations

Feature 4: Altered level of consciousness - normal to comatose

Levels of consciousness

Agitated (out of control)

Hyperalert (vigilant)

Alert (normal)

Drowsy (lethargic)

Obtunded (difficult to wake)

Stuporous (v. difficult to wake)

Comatose (unable to wake)

http://www.icudelirium.org/docs/CAM_ICU_training.pdf

van den Boogaard et al. BMJ 2012

Using the PRE-DELIRIC:PREdiction of DELIRium in ICu patients

Diagnosis of delirium:Differentiating it from mental illness

Age of onset and history of mental illness

Assess risk factors for delirium

Disorientation

Reduced level of alertness and fluctuations

Speech not typically dysarthric in mental illness (except in intoxication or withdrawal)

Visual hallucinations are atypical

Algahtani and Abdu. Neurosciences 17(3) 205 (2012)

Diagnosis of delirium:Differentiating it from dementia

Delirum Dementia

Attention impaired intact early, impaired late

Course acute, fluctuating chronic, progressive

Speech rambling, mumbling impoverished

Perception illusions and hallucinations often normal

Thinking disorganized impoverished

Alertness agitated/obtunded normal

Clinical case:79 y/o with confusion

A 79 y/o male who is being treated for a pneumonia is referred to psychiatry consults for after waking up at night screaming and disoriented. The consult resident establishes that the patient’s attention is poor, their memory is impaired, and their speech and behavior is disorganized. They believe he is delirious and are considering treatment with haloperidol.

Questions:1)What is the KEY historical point missing?2)What should be done before recommending haloperidol?

Etiology, pathophysiology and clinical assessment of delirium

Etiology:General principles

Trying to establish and etiology of delirium is essential

Often multifactorial

Take heed of the vulnerable patient!- always think about the vulnerability X exposure interaction

The most important graph in medicine

High

Risk

Exp

osu

re

Low

Low

High

Sick

Not sick

Etiology of delirium:Risks

Age, age, age and age

Cognitive dysfunction- intellectual disabilities, visual impairment, depression, dementia

Prior neuropathology- stroke, tumor, vasculitis, trauma, history of trauma

Major medical/surgical illness- hip fracture, ICU stays,

Algahtani and Abdu. Neurosciences 17(3) 205 (2012)

Etiology of delirium:Exposures

Metabolic and systemic illness- sepsis, organ failure, electrolyte abnormalities, hypoxia, hypoglycemia, UTI

Endocrinopathies

CNS infections and lesions

Nutritional deficiencies- thiamine, niacin, B12, folate

Intoxication and withdrawal

Others…- heat stoke, electrocution, sleep deprivation, MEDICATIONS

Etiology of delirium:Medications

Anticholinergics/antihistamines

Analgesics

Steroids/sympathomimetics

Sedatives

Anticonvulsants

Antiarrythmics/antihypertensives

Antibiotics (PCN, cephalosporins, quiolones)

“I watch death”

Note the mnemonic “WHHHIMP”

Etiology of delirium:Life threatening causes

Wernicke’s encephalopathy

Hypoxia

Hypoglycemia

Hypertensive encephalopathy

Intracerebral hemorrhage

Meningitis/encephalitis

Poisoning

Pathophysiology of delirium:Several hypotheses

Neurotransmitter hypothesis- hypocholinergic state

i. supported by deliriogenic effects of anticholinergic medications and dementia

- dopamine (and norepinephrine) excessii. supported by intoxicating effects of numerous dopaminergic

agonists and the beneficial effects of antipsychotics

Neuroinflammatory hypothesis- elevated cortisol, elevated CRP, elevated procalcitonin

- alteration of the BBB and microglia activation disrupts brain function

Hypoxia hypothesis- disrupted oxygen supply or neurovascular coupling causing

neuronal dysfunction

Neurovascular coupling

Hughes, Patel and Pandharipande. Curr Opinion in Critical Care 2012

Examples of neuropathology associated with delirium

CT MRI

White matter hyperintensities Atrophy

Neuroimaging in delirium:Not generally recommended

Structural changes- atrophy

- vascular lesions and white matter hyperintesities

- white matter changes (evaluated with diffusion tensor MRI)

Perfusion/metabolic changes- Reduced blood flow (SPECT imaging)

- Reduced metabolism (PET imaging)

EEG- diffuse slowing with moderate amplitude common but nonspecific

- useful in ruling out non-convulsive status epilepticus, hepatic encephalopathy (triphasic waves) and some viral encephalopathies

Fox et al. PNAS 2005

Functional MRI:Defining large networks potentially disrupted in delirium

Clinical assessment of delirium:General principles

Review chart for fluctuating course, recent illness, baseline function

Review medications including PRNs

Review history of substance use, CNS pathology and mental illness

Gather collateral with emphasis on recent change in function

Physical exam findings in delirium

Hypotension- dehydration, sepsis, cardiac disease

Tachycardia- dehydration, sepsis, cardiac disease, hyperthyroidism, intoxication

Fever- infection, withdrawal states, NMS

Hypothermia- sepsis, myxedema, Wernicke’s encephalopathy

Fayes et al. J Pain Symptom Manage 30: 41 (2005)

Using the MMSE in delirium

Scores < 24 have been suggested to be a threshold

4 key questions of the MMSE- Year

- Date

- Backward spelling (“DLROW”)

- Figure copying

Clinical assessment of delirium:Laboratory tests

Recommended tests- Electrolytes, glucose, calcium, CBC, LFTs, UA, Utox and drug levels

when appropriate

Not necessarily recommended, but should be considered

- CXR, blood cultures, blood gasses, EEG

Use only in appropriate cases- Neuroimaging (structural with CT or MRI, functional with PET or

SPECT)

Clinical case:24 y/o with acute confusion

A 24 y/o male with history of bipolar disorder presents to the ED on a hot Seattle summer day with acute confusion, agitation, and aggressive behavior. He is hyperthermic and has various routine laboratory abnormalities including elevated WBCs and hypernatremia. Although poorly cooperative with the exam you note some rigidity, tremor, tachycardia, diaphoresis, and tachypnea.

Questions:1)What other labs would you like to know?2)What is a possible diagnosis?

Treatment, prevention and prognosis of delirium

Management:Basic principles

Search for the underlying cause!- Medications only treat symptoms, not etiology.

Minimize psychoactive medications

Provide supportive care- oxygen, hydration and nutrition

- positioning and mobilization

- avoid restraints

- maximize non-pharmacologic care

The goal is an alert and manageable patent, not a sedated and lethargic patient

Treating delirium:Non-pharmacologic approaches

Promote sleep hygiene- visible clock, provide light cycle, avoid night time awakenings

Low stimuli environment- reduce IV “beeps”, move away from the nursing station

Encourage family visits, consistent staffing

Minimize interrupting patient and unnecessary moves/tests

Inouye et al., A multicomponent intervention to prevent delirium in hospitalized older patients.

N Engl J Med, 1999. 340(9): p. 669-76.

Pharmacologic treatment of delirium:Use only if patient is dangerous or physically/mentally uncomfortable

Haloperidol is first line- not if concern for Parkinson’s, Lewy body or Parkinson’s Plus

syndrome

- start with 0.5 mg BID PO/IV with 0.5 mg q4 hours PRN

- IV may cause less EPS but it has a short duration of actions

Atypical antipsychotics (no IV forms)- Risperidone: start at 0.25-0.5 mg PO BID

- Olanzapine: start 2.5-5 mg PO BID (IM form available)

- Quetiapine: start at 12.5-25 mg BID (often preferred given low risk of EPS, can cause orthostasis)

- All can cause metabolic syndrome if used long term and acutely disrupt glucose management complicating diabetes treatment

Pharmacologic treatment of delirium:Guidelines regarding QTc prolongation

Potentially causing V-fib/Torsades des pointes- men: < 430 normal, 431 - 450 increased, > 451 high

- women: < 450 normal, 451 - 470 increased, > 471 high

- watch for an increase of > 30 msec from baseline

Contributing factors include- age, female gender, hx of heart disease, CHF, hepatic disease

- low K/Mg, bradycardia, alcohol use, drug use (stimulants), rapid infusion of drugs

Antipsychotics to be leery of:- Typical : pimozide, thioridazine, IV haloperidol

- Atypical : ziprasidone > quetiapine > risperidone (newer agents also)

Clinical case:24 y/o with odd behavior

A 24 y/o male with a history of schizophrenia presents with fluctuating behavior and cognitive disorganization that is different from his baseline. He is intermittently mute, postures while standing, resists movements (negativism), and engages in echolalia and echopraxia. At times he is conversant, at others fully unresponsive.

Questions:1) Is this delirium or catatonia?2) What medications might be helpful?

Clinical case:Catatonic symptoms in delirium

Catatonia has 3 or more of the following- stupor, catalepsy, waxy flexibility, mutism, negativism, posturing,

mannerisms, stereotypy, agitation, grimacing, echolalia, echopraxia

Catatonia can occur in any mental or medical disorder but should NOT be attributed exclusively to delirium

Catatonia is frequently treated with benzodiazepines which can worsen delirium

Recommendation: resolve delirium first, then deal with catatonia if it remains

Prognosis:General considerations

Will continue until the underlying cause resolves

Typically resolves in days, but can take substantially longer in those with known CNS disease

Subsyndromal symptoms can return, even after days, and caretakers should be informed

Clinical case:24 y/o with agitation and psychosis

A 24 y/o women with a history of depression is brought to the ED because of increasing disorganization and hostility. She is intermittently communicative, and when speaking is pressured and preoccupied with being chosen by god to save the world. At other times he stares off into space, mute while performing odd gestures with her hands. At other times she is tearful, angry and accuses her family of trying to poison her.

Questions:1) What is odd about this presentation?2) Why is the history of depression important here?3) What is a possible diagnosis?

Jacobowski et al. Journal of Psychiatric Practice. 19(1):15 (2013)

Clinical case:Delirious mania (Bell’s Mania)

Delirium may be present in 10-20% of manic patients

Acute onset of both manic and delirium symptoms

- psychosis and catatonic symptoms are also common

Difficult to treat with antipsychotics and mood stabilizers

ECT and benzodiazepines seem most effective

As always….rule out all medical causes of delirium

Essential take home points

Delirium is common and represents the brain under stress

Establish the patients baseline function

Always review medication and substance use

Search for an etiology and rectify

Use antipsychotics only when necessary, behavioral measures should be used first