177 Gait Disorders, Imbalance, and Falls CHAPTER 26

TABLE 26-3 Meta-Analysis of Risk Factors for Falls in Older Persons

RISK FACTOR MEAN RR (OR) RANGE

Muscle weakness 4.4 1.5–10.3

History of falls 3.0 1.7–7.0

Gait deficit 2.9 1.3–5.6

Balance deficit 2.9 1.6–5.4

Use assistive device 2.6 1.2–4.6

Visual deficit 2.5 1.6–3.5

Arthritis 2.4 1.9–2.9

Impaired ADL 2.3 1.5–3.1

Depression 2.2 1.7–2.5

Cognitive impairment 1.8 1.0–2.3

Age >80 years 1.7 1.1–2.5

Abbreviations: ADL, activity of daily living; OR, odds ratio from retrospective studies;

RR, relative risk from prospective studies.

Source: Reproduced with permission from Guideline for the Prevention of Falls in

Older Persons. J Am Geriatr Soc 49:664, 2001.

■ ASSESSMENT OF THE PATIENT WITH FALLS

The most productive approach is to identify the high-risk patient

prospectively, before there is a serious injury. All community-dwelling

adults should be asked annually about falls and whether or not fear

of falling limits daily activities. The Timed Up and Go (“TUG”) test

involves timing a patient as they stand up from a chair, walk 10 feet,

turn, and then sit down. Patients with a history of falls or those requiring >12 s to complete the TUG test are at high risk for falls and should

undergo further assessment.

History The history surrounding a fall is often problematic or

incomplete, and the underlying mechanism or cause may be difficult to

establish in retrospect. Patients should be queried about any provoking

factors (including head turn, standing) or prodromal symptoms, such

as dizziness, vertigo, presyncopal symptoms, or focal weakness. A history of baseline mobility and medical comorbidities should be elicited.

Patients at particular risk include those with mental status changes or

dementia. Medications should be reviewed, with particular attention

to benzodiazepines, opioids, antipsychotics, antiepileptics, antidepressants, antiarrhythmics, and diuretics, all of which are associated with

an increased risk of falls. It is equally important to distinguish mechanical falls (those caused by tripping or slipping) due to purely extrinsic

or environmental factors from those in which a modifiable intrinsic

factor contributes. Recurrent falls may indicate an underlying gait or

balance disorder. Falls associated with loss of consciousness (syncope,

seizure) may require appropriate cardiac or neurologic evaluation and

intervention (Chaps. 21 and 425), although a patient’s report of change

in consciousness may be unreliable.

Physical Examination Examination of the patient with falls

should include a basic cardiac examination, including orthostatic

blood pressure if indicated by history, and observation of any orthopedic abnormalities. Mental status is easily assessed while obtaining

a history from the patient; the remainder of the neurologic examination should include visual acuity, strength and sensation in the lower

extremities, muscle tone, and cerebellar function, with particular attention to gait and balance as described earlier in this chapter.

Fall Patterns The description of a fall event may provide further

clues to the underlying etiology. While there is no standard nosology

of falls, some common clinical patterns may emerge and provide a clue.

DROP ATTACKS AND COLLAPSING FALLS Drop attacks and collapsing

falls are associated with a sudden loss of postural tone. Patients may

report that their legs just “gave out” underneath them or that they

“collapsed in a heap.” Syncope or orthostatic hypotension may be a

factor in some such falls. Neurologic causes are relatively rare but

include atonic seizures, myoclonus, and intermittent obstruction of the

foramen of Monro by a colloid cyst of the third ventricle causing acute

obstructive hydrocephalus. An emotional trigger suggests cataplexy.

While collapsing falls are more common among older patients with

vascular risk factors, drop attacks should not be confused with vertebrobasilar ischemic attacks.

TOPPLING FALLS Some patients maintain tone in antigravity muscles

but fall over like a tree trunk, as if postural defenses had disengaged.

Causes include cerebellar pathology and lesions of the vestibular system. There may be a consistent direction to such falls. Toppling falls are

an early feature of progressive supranuclear palsy, and a late feature of

Parkinson’s disease, once postural instability has developed. Thalamic

lesions causing truncal instability (thalamic astasia) may also contribute to this type of fall.

FALLS DUE TO GAIT FREEZING Freezing of gait is seen in Parkinson’s

disease and related disorders. The feet stick to the floor and the center

of mass keeps moving, resulting in a disequilibrium from which the

patient has difficulty recovering, resulting in a forward fall. Similarly,

patients with Parkinson’s disease and festinating gait may find their feet

unable to keep up and may thus fall forward.

FALLS RELATED TO SENSORY LOSS Patients with somatosensory, visual,

or vestibular deficits are prone to falls. These patients have particular

difficulty dealing with poor illumination or walking on uneven ground.

They often report subjective imbalance, apprehension, and fear of falling. These patients may be especially responsive to a rehabilitation-based

intervention.

FALLS RELATED TO WEAKNESS Patients who lack strength in antigravity muscles have difficulty rising from a chair or maintaining their balance after a perturbation. These patients are often unable to get up after

a fall and may have to remain on the floor for a prolonged period until

help arrives. If due to deconditioning, this is often treatable. Resistance

strength training can increase muscle mass and leg strength, even for

people in their eighties and nineties.

TREATMENT

Interventions to Reduce the Risk of Falls and Injury

Efforts should be made to define the mechanism underlying falls

in a given patient, as specific treatment may be possible once a

diagnosis is established. Orthostatic changes in blood pressure

and pulse should be recorded. Medications (including over-thecounter) should be reviewed, reevaluating benefits and burdens

of medications that might increase fall risk. Treatment of cataracts

and avoidance of multifocal lenses could be considered for patients

whose falls result from vision impairment. A home visit to look

for environmental hazards can be helpful. A variety of modifications may be recommended to improve safety, including improved

lighting, installation of grab bars and nonslip surfaces, and use of

adaptive equipment.

Home- and group-based exercise programs focusing on leg

strength and balance, physical therapy, and use of assistive devices

reduce fall risk in individuals with a history of falls or disorders

of gait and balance. Rehabilitative interventions aim to improve

muscle strength and balance stability and to make the patient more

resistant to injury. High-intensity resistance strength training with

weights and machines is useful to improve muscle mass, even in

frail older patients. Improvements realized in posture and gait

should translate to reduced risk of falls and injury. Sensory balance training is another approach to improving balance stability.

Measurable gains can be made in a few weeks of training, and

benefits can be maintained over 6 months by a 10- to 20-min home

exercise program. This strategy is particularly successful in patients

with vestibular and somatosensory balance disorders. The National

Institute on Aging provides online examples of balance exercises for

older adults. A Tai Chi exercise program has been demonstrated to

reduce the risk of falls and injury in patients with Parkinson’s disease. Cognitive training, including dual-task training, may improve

mobility in older adults with cognitive impairment.

178 PART 2 Cardinal Manifestations and Presentation of Diseases

Confusion, a mental and behavioral state of reduced comprehension, coherence, and capacity to reason, is one of the most common

problems encountered in medicine, accounting for a large number of

emergency department visits, hospital admissions, and inpatient consultations. Delirium, a term used to describe an acute confusional state,

remains a major cause of morbidity and mortality, costing billions of

dollars yearly in health care costs in the United States alone. Despite

increased efforts targeting awareness of this condition, delirium often

goes unrecognized in the face of evidence that it is usually the cognitive

manifestation of serious underlying medical or neurologic illness.

■ CLINICAL FEATURES OF DELIRIUM

A multitude of terms are used to describe patients with delirium,

including encephalopathy, acute brain failure, acute confusional state,

and postoperative or intensive care unit (ICU) psychosis. Delirium

has many clinical manifestations, but it is defined as a relatively

acute decline in cognition that fluctuates over hours or days. The

hallmark of delirium is a deficit of attention, although all cognitive

domains—including memory, executive function, visuospatial tasks,

and language—are variably involved. Associated symptoms that may be

present in some cases include altered sleep-wake cycles, perceptual disturbances such as hallucinations or delusions, affect changes, and autonomic findings that include heart rate and blood pressure instability.

Delirium is a clinical diagnosis that is made only at the bedside. Two

subtypes have been described—hyperactive and hypoactive—based on

differential psychomotor features. The cognitive syndrome associated

with severe alcohol withdrawal (i.e., “delirium tremens”) remains

the classic example of the hyperactive subtype, featuring prominent

hallucinations, agitation, and hyperarousal, often accompanied by

life-threatening autonomic instability. In striking contrast is the hypoactive subtype, exemplified by benzodiazepine intoxication, in which

patients are withdrawn and quiet, with prominent apathy and psychomotor slowing.

This dichotomy between subtypes of delirium is a useful construct,

but patients often fall somewhere along a spectrum between the

hyperactive and hypoactive extremes, sometimes fluctuating from one

to the other. Therefore, clinicians must recognize this broad range of

presentations of delirium to identify all patients with this potentially

27 Confusion and Delirium

S. Andrew Josephson, Bruce L. Miller

Acknowledgements

I am grateful to Dr. Lewis R. Sudarsky for his substantial contributions to

earlier versions of this chapter.

■ FURTHER READING

American Geriatrics Society, British Geriatrics Society,

American Academy of Orthopedic Surgeons Panel on Falls

Prevention: Guideline for the prevention of falls in older persons.

J Am Geriatr Soc 49:664, 2001.

Ganz D, Latham N: Prevention of falls in community-dwelling older

adults. N Engl J Med 382:734, 2020.

National Institute on Aging: Exercise and Physical Activity. Available from https://www.nia.nih.gov/health/exercise-physicalactivity. Accessed April 25, 2021.

Nutt JG: Classification of gait and balance disorders. Adv Neurol

87:135, 2001.

Pirker W, Katzenschlager R: Gait disorders in adults and the

elderly. Wien Klin Wochenschr 129:81, 2017.

reversible cognitive disturbance. Hyperactive patients are often easily

recognized by their characteristic severe agitation, tremor, hallucinations, and autonomic instability. Patients who are quietly hypoactive

are more often overlooked on the medical wards and in the ICU.

The reversibility of delirium is emphasized because many etiologies,

such as infection and medication effects, can be treated easily. The

long-term cognitive consequences of delirium remain an area of active

research. Some episodes of delirium continue for weeks, months, or

even years. The persistence of delirium in some patients and its high

recurrence rate may be due to inadequate initial treatment of the

underlying etiology. In other instances, delirium appears to cause permanent neuronal damage and long-term cognitive decline. Therefore,

prevention strategies are important to implement. Even if an episode

of delirium completely resolves, there may be lingering effects of the

disorder; a patient’s recall of events after delirium varies widely, ranging

from complete amnesia to repeated reexperiencing of the frightening

period of confusion, similar to what is seen in patients with posttraumatic stress disorder.

■ RISK FACTORS

An effective primary prevention strategy for delirium begins with

identification of high-risk patients. Some hospital systems have initiated comprehensive delirium programs that screen most or all patients

upon admission or before elective surgery; positive screens trigger a

host of focused prevention measures. Multiple validated scoring systems have been developed as a screen for asymptomatic patients, many

of which emphasize well-established risk factors for delirium.

The two most consistently identified risk factors are older age and

baseline cognitive dysfunction. Individuals who are aged >65 or exhibit

low scores on standardized tests of cognition develop delirium upon

hospitalization at a rate approaching 50%. Whether age and baseline

cognitive dysfunction are truly independent risk factors is uncertain.

Other predisposing factors include sensory deprivation, such as preexisting hearing and visual impairment, as well as indices for poor overall

health, including baseline immobility, malnutrition, and underlying

medical or neurologic illness.

In-hospital risks for delirium include the use of bladder catheterization, physical restraints, sleep and sensory deprivation, and the addition of three or more new medications. Avoiding such risks remains a

key component of delirium prevention as well as treatment. Surgical

and anesthetic risk factors for the development of postoperative delirium include procedures such as those involving cardiopulmonary

bypass, inadequate or excessive treatment of pain in the immediate

postoperative period, and perhaps specific agents such as inhalational

anesthetics.

The relationship between delirium and dementia (Chap. 29) is complicated by significant overlap between the two conditions, and it is not

always simple to distinguish between them. Dementia and preexisting

cognitive dysfunction serve as major risk factors for delirium, and at

least two-thirds of cases of delirium occur in patients with coexisting

underlying dementia. A form of dementia with parkinsonism, dementia with Lewy bodies (Chap. 434), is characterized by a fluctuating

course, prominent visual hallucinations, parkinsonism, and an attentional deficit that clinically resembles hyperactive delirium; patients

with this condition are particularly vulnerable to delirium. Delirium in

the elderly often reflects an insult to a brain that is vulnerable due to an

underlying neurodegenerative condition. Therefore, the development

of delirium sometimes heralds the onset of a previously unrecognized

brain disorder, and after the acute delirious episode has cleared, careful

screening for an underlying condition should occur in the outpatient

setting.

■ EPIDEMIOLOGY

Delirium is common, but its reported incidence has varied widely with

the criteria used to define this disorder. Estimates of delirium in hospitalized patients range from 10% to >50%, with higher rates reported for

elderly patients and patients undergoing hip surgery. Older patients in

the ICU have especially high rates of delirium that approach 75%. The

179Confusion and Delirium CHAPTER 27

APPROACH TO THE PATIENT

Delirium

Because the diagnosis of delirium is clinical and is made at the

bedside, a careful history and physical examination are necessary in

evaluating patients with possible confusional states. Screening tools

can aid physicians and nurses in identifying patients with delirium,

including the Confusion Assessment Method (CAM); the Nursing

Delirium Screening Scale (NuDESC); the Organic Brain Syndrome

Scale; the Delirium Rating Scale; and, in the ICU, the ICU version

of the CAM and the Delirium Detection Score. Using the wellvalidated CAM, a diagnosis of delirium is made if there is (1) an

acute onset and fluctuating course and (2) inattention accompanied by either (3) disorganized thinking or (4) an altered level of

consciousness (Table 27-1). These scales may not identify the full

spectrum of patients with delirium, and all patients who are acutely

confused should be presumed delirious regardless of their presentation due to the wide variety of possible clinical features. A course

that fluctuates over hours or days and may worsen at night (termed

sundowning) is typical but not essential for the diagnosis. Observation will usually reveal an altered level of consciousness or a deficit

of attention. Other features that are sometimes present include

alteration of sleep-wake cycles, thought disturbances such as hallucinations or delusions, autonomic instability, and changes in affect.

HISTORY

It may be difficult to elicit an accurate history in delirious patients

who have altered levels of consciousness or impaired attention.

Information from a collateral source such as a spouse or another

family member is therefore invaluable. The three most important

pieces of history are the patient’s baseline cognitive function, the

time course of the present illness, and current medications.

Premorbid cognitive function can be assessed through the collateral source or, if needed, via a review of outpatient records.

Delirium by definition represents a change that is relatively acute

and usually developing over hours to days, from a cognitive baseline. An acute confusional state is nearly impossible to diagnose

without some knowledge of baseline cognitive function. Without

condition is not recognized in up to one-third of delirious inpatients,

and the diagnosis is especially problematic in the ICU environment,

where cognitive dysfunction is often difficult to appreciate in the

setting of serious systemic illness and sedation. Delirium in the ICU

should be viewed as an important manifestation of organ dysfunction

not unlike liver, kidney, or heart failure. Outside the acute hospital

setting, delirium occurs in nearly one-quarter of patients in nursing

homes and in 50–80% of those at the end of life. These estimates

emphasize the remarkably high frequency of this cognitive syndrome

in older patients, a population that continues to grow.

An episode of delirium was previously viewed as a transient condition that carried a benign prognosis. It is now recognized as a disorder

with substantial morbidity and mortality, and that often represents

the first manifestation of a serious underlying illness. Estimates of

in-hospital mortality rates among delirious patients range from 25%

to 33%, similar to mortality rates due to sepsis. Patients with an inhospital episode of delirium have a fivefold higher mortality rate in

the months after their illness compared with age matched nondelirious

hospitalized patients. Delirious hospitalized patients also have a longer

length of stay, are more likely to be discharged to a nursing home, have

a higher frequency of readmission, and are more likely to experience

subsequent episodes of delirium and cognitive decline; as a result, this

condition has an enormous economic cost.

■ PATHOGENESIS

The pathogenesis and anatomy of delirium are incompletely understood. The attentional deficit that serves as the neuropsychological

hallmark of delirium has a diffuse localization within the brainstem,

thalamus, prefrontal cortex, and parietal lobes. Rarely, focal lesions

such as ischemic strokes have led to delirium in otherwise healthy

persons; right parietal and medial dorsal thalamic lesions have been

reported most commonly, pointing to the importance of these areas in

delirium pathogenesis. In most cases, however, delirium results from

widespread disturbances in cortical and subcortical regions of the

brain. Electroencephalogram (EEG) usually reveals symmetric slowing, a nonspecific finding that supports diffuse cerebral dysfunction.

Multiple neurotransmitter abnormalities, proinflammatory factors,

and specific genes likely play a role in the pathogenesis of delirium.

Deficiency of acetylcholine may play a key role, and medications

with anticholinergic properties can commonly precipitate delirium.

As noted earlier, patients with preexisting dementia are particularly

susceptible to episodes of delirium. Alzheimer’s disease (Chap. 431),

dementia with Lewy bodies (Chap. 434), and Parkinson’s disease

dementia (Chap. 435) are all associated with cholinergic deficiency

due to degeneration of acetylcholine-producing neurons in the basal

forebrain. In addition, other neurotransmitters are also likely to be

involved in this diffuse cerebral disorder. For example, increases in

dopamine can lead to delirium, and patients with Parkinson’s disease

treated with dopaminergic medications can develop a delirium-like

state that features visual hallucinations, fluctuations, and confusion.

Not all individuals exposed to the same insult will develop signs of

delirium. A low dose of an anticholinergic medication may have no

cognitive effects on a healthy young adult but produce a florid delirium in an elderly person with known underlying dementia, although

even healthy young persons develop delirium with very high doses

of anticholinergic medications. This concept of delirium developing

as the result of an insult in predisposed individuals is currently the

most widely accepted pathogenic construct. Therefore, if a previously

healthy individual with no known history of cognitive illness develops

delirium in the setting of a relatively minor insult such as elective

surgery or hospitalization, an unrecognized underlying neurologic

illness such as a neurodegenerative disease, multiple previous strokes,

or another diffuse cerebral cause should be considered. In this context,

delirium can be viewed as a “stress test for the brain” whereby exposure

to known inciting factors such as systemic infection and offending

drugs can unmask a decreased cerebral reserve and herald a serious

underlying and potentially treatable illness. New blood-based biomarkers for specific dementias may soon be available to help predict people

at risk for delirium before surgical procedures or hospitalization.

TABLE 27-1 The Confusion Assessment Method (CAM) Diagnostic

Algorithma

The diagnosis of delirium requires the presence of features 1 and 2 and either

feature 3 or 4.

Feature 1. Acute Onset and Fluctuating Course

This feature is satisfied by positive responses to the following questions: Is there

evidence of an acute change in mental status from the patient’s baseline? Did

the (abnormal) behavior fluctuate during the day, that is, tend to come and go, or

did it increase and decrease in severity?

Feature 2. Inattention

This feature is satisfied by a positive response to the following question: Did the

patient have difficulty focusing attention, for example, being easily distractible,

or have difficulty keeping track of what was being said?

Feature 3. Disorganized Thinking

This feature is satisfied by a positive response to the following question: Was

the patient’s thinking disorganized or incoherent, such as rambling or irrelevant

conversation, unclear or illogical flow of ideas, or unpredictable switching from

subject to subject?

Feature 4. Altered Level of Consciousness

This feature is satisfied by any answer other than “alert” to the following

question: Overall, how would you rate the patient’s level of consciousness: alert

(normal), vigilant (hyperalert), lethargic (drowsy, easily aroused), stupor (difficult

to arouse), or coma (unarousable)?

a

Information is usually obtained from a reliable reporter, such as a family member,

caregiver, or nurse.

Source: From Annals of Internal Medicine, SK Inouye et al: Clarifying confusion: The

Confusion Assessment Method. A new method for detection of delirium. 113(12):941,

1990. Copyright © 1990 American College of Physicians. All Rights Reserved.

Reprinted with the permission of American College of Physicians, Inc.

180 PART 2 Cardinal Manifestations and Presentation of Diseases

this information, many patients with dementia or longstanding

depression may be mistaken as delirious during a single initial

evaluation. Patients with a more hypoactive, apathetic presentation

with psychomotor slowing may be identified as being different from

baseline only through conversations with family members. A number of validated instruments have been shown to diagnose cognitive

dysfunction accurately using a collateral source, including the modified Blessed Dementia Rating Scale and the Clinical Dementia Rating (CDR). Baseline cognitive impairment is common in patients

with delirium. Even when no such history of cognitive impairment

is elicited, there should still be a high suspicion for a previously

unrecognized underlying neurologic disorder.

Establishing the time course of cognitive change is important not

only to make a diagnosis of delirium but also to correlate the onset

of the illness with potentially treatable etiologies such as recent

medication changes or symptoms of systemic infection.

Medications remain a common cause of delirium, especially

compounds with anticholinergic or sedative properties. It is estimated that nearly one-third of all cases of delirium are secondary to

medications, especially in the elderly. Medication histories should

include all prescription as well as over-the-counter and herbal

substances taken by the patient and any recent changes in dosing

or formulation, including substitution of generics for brand-name

medications.

Other important elements of the history include screening for

symptoms of organ failure or systemic infection, which often

contributes to delirium in the elderly. A history of illicit drug use,

alcoholism, or toxin exposure is common in younger delirious

patients. Finally, asking the patient and collateral source about other

symptoms that may accompany delirium, such as depression, may

help identify potential therapeutic targets.

PHYSICAL EXAMINATION

The general physical examination in a delirious patient should

include careful screening for signs of infection such as fever, tachypnea, pulmonary consolidation, heart murmur, and meningismus. The patient’s fluid status should be assessed; both dehydration

and fluid overload with resultant hypoxemia have been associated

with delirium, and each is usually easily rectified. The appearance

of the skin can be helpful, showing jaundice in hepatic encephalopathy, cyanosis in hypoxemia, or needle tracks in patients using

intravenous drugs.

The neurologic examination requires a careful assessment of

mental status. Patients with delirium often present with a fluctuating course; therefore, the diagnosis can be missed when one relies

on a single time point of evaluation. For patients who worsen in the

evening (sundowning), assessment only during morning rounds

may be falsely reassuring.

An altered level of consciousness ranging from hyperarousal

to lethargy to coma is present in most patients with delirium and

can be assessed easily at the bedside. In a patient with a relatively

normal level of consciousness, a screen for an attentional deficit is

in order, because this deficit is the classic neuropsychological hallmark of delirium. Attention can be assessed while taking a history

from the patient. Tangential speech, a fragmentary flow of ideas, or

inability to follow complex commands often signifies an attentional

problem. There are formal neuropsychological tests to assess attention, but a simple bedside test of digit span forward is quick and

fairly sensitive. In this task, patients are asked to repeat successively

longer random strings of digits beginning with two digits in a row,

said to the patient at one per second intervals. Healthy adults can

repeat a string of five to seven digits before faltering; a digit span of

four or less usually indicates an attentional deficit unless hearing or

language barriers are present, and many patients with delirium have

digit spans of three or fewer digits.

More formal neuropsychological testing can be helpful in assessing a delirious patient, but it is usually too cumbersome and

time-consuming in the inpatient setting. A Mini-Mental State

Examination (MMSE) provides information regarding orientation,

language, and visuospatial skills (Chap. 29); however, performance

of many tasks on the MMSE, including the spelling of “world” backward and serial subtraction of digits, will be impaired by delirious

patients’ attentional deficits, rendering the test unreliable.

The remainder of the screening neurologic examination should

focus on identifying new focal neurologic deficits. Focal strokes

or mass lesions in isolation are rarely the cause of delirium, but

patients with underlying extensive cerebrovascular disease or neurodegenerative conditions may not be able to cognitively tolerate

even relatively small new insults. Patients should be screened for

other signs of neurodegenerative conditions such as parkinsonism,

which is seen not only in idiopathic Parkinson’s disease but also in

other dementing conditions including Alzheimer’s disease, dementia with Lewy bodies, and progressive supranuclear palsy. The presence of multifocal myoclonus or asterixis on the motor examination

is nonspecific but usually indicates a metabolic or toxic etiology of

the delirium.

ETIOLOGY

Some etiologies can be easily discerned through a careful history

and physical examination, whereas others require confirmation with

laboratory studies, imaging, or other ancillary tests. A large, diverse

group of insults can lead to delirium, and the cause in many patients

is multifactorial. Common etiologies are listed in Table 27-2.

Prescribed, over-the-counter, and herbal medications all can precipitate delirium. Drugs with anticholinergic properties, narcotics,

and benzodiazepines are particularly common offenders, but nearly

any compound can lead to cognitive dysfunction in a predisposed

patient. Whereas an elderly patient with baseline dementia may

become delirious upon exposure to a relatively low dose of a medication, in less susceptible individuals, delirium occurs only with

very high doses of the same medication. This observation emphasizes the importance of correlating the timing of recent medication

changes, including dose and formulation, with the onset of cognitive dysfunction.

In younger patients, illicit drugs and toxins are common causes

of delirium. In addition to more classic drugs of abuse, the availability of “bath salts,” synthetic cannabis (Chap. 455), methylenedioxymethamphetamine (MDMA, ecstasy), γ-hydroxybutyrate

(GHB), and the phencyclidine (PCP)-like agent ketamine has led

to an increase in delirious young persons presenting to acute care

settings (Chap. 457). Many common prescription drugs such as

oral narcotics and benzodiazepines are often abused and readily

available on the street. Alcohol abuse leading to high serum levels

causes confusion, but more commonly, it is withdrawal from alcohol that leads to a hyperactive delirium (Chap. 453). Alcohol and

benzodiazepine withdrawal should be considered in all cases of

delirium, including in the elderly, because even patients who drink

only a few servings of alcohol every day can experience relatively

severe withdrawal symptoms upon hospitalization.

Metabolic abnormalities such as electrolyte disturbances of

sodium, calcium, magnesium, or glucose can cause delirium, and

mild derangements can lead to substantial cognitive disturbances

in susceptible individuals. Other common metabolic etiologies

include liver and renal failure, hypercarbia and hypoxemia, vitamin

deficiencies of thiamine and B12, autoimmune disorders including

central nervous system (CNS) vasculitis, and endocrinopathies

such as thyroid and adrenal disorders.

Systemic infections often cause delirium, especially in the elderly.

A common scenario involves the development of an acute cognitive

decline in the setting of a urinary tract infection in a patient with

baseline dementia. Pneumonia, skin infections such as cellulitis,

and frank sepsis also lead to delirium. This so-called septic encephalopathy, often seen in the ICU, is probably due to the release of

proinflammatory cytokines and their diffuse cerebral effects. CNS

infections such as meningitis, encephalitis, and abscess are less

common etiologies of delirium, as are cases of autoimmune or

181Confusion and Delirium CHAPTER 27

TABLE 27-2 Differential Diagnosis of Delirium

Toxins

Prescription medications: especially those with anticholinergic properties,

narcotics, and benzodiazepines

Drugs of abuse: alcohol intoxication and alcohol withdrawal, opiates, ecstasy,

LSD, GHB, PCP, ketamine, cocaine, “bath salts,” marijuana and its synthetic

forms

Poisons: inhalants, carbon monoxide, ethylene glycol, pesticides

Metabolic Conditions

Electrolyte disturbances: hypoglycemia, hyperglycemia, hyponatremia,

hypernatremia, hypercalcemia, hypocalcemia, hypomagnesemia

Hypothermia and hyperthermia

Pulmonary failure: hypoxemia and hypercarbia

Liver failure/hepatic encephalopathy

Renal failure/uremia

Cardiac failure

Vitamin deficiencies: B12, thiamine, folate, niacin

Dehydration and malnutrition

Anemia

Infections

Systemic infections: urinary tract infections, pneumonia, skin and soft tissue

infections, sepsis

CNS infections: meningitis, encephalitis, brain abscess

Endocrine Conditions

Hyperthyroidism, hypothyroidism

Hyperparathyroidism

Adrenal insufficiency

Cerebrovascular Disorders

Global hypoperfusion states

Hypertensive encephalopathy

Focal ischemic strokes and hemorrhages (rare): especially nondominant parietal

and thalamic lesions

Autoimmune Disorders

CNS vasculitis

Cerebral lupus

Neurologic paraneoplastic and autoimmune encephalitis

Seizure-Related Disorders

Nonconvulsive status epilepticus

Intermittent seizures with prolonged postictal states

Neoplastic Disorders

Diffuse metastases to the brain

Gliomatosis cerebri

Carcinomatous meningitis

CNS lymphoma

Hospitalization

Terminal end-of-life delirium

Abbreviations: CNS, central nervous system; GHB, γ-hydroxybutyrate; LSD, lysergic

acid diethylamide; PCP, phencyclidine.

Cerebrovascular etiologies of delirium are usually due to global

hypoperfusion in the setting of systemic hypotension from heart

failure, septic shock, dehydration, or anemia. Focal strokes in the

right parietal lobe and medial dorsal thalamus rarely can lead to

a delirious state. A more common scenario involves a new focal

stroke or hemorrhage causing confusion in a patient who has

decreased cerebral reserve. In these individuals, it is sometimes

difficult to distinguish between cognitive dysfunction resulting

from the new neurovascular insult itself and delirium due to the

infectious, metabolic, and pharmacologic complications that can

accompany hospitalization after stroke.

Because a fluctuating course often is seen in delirium, intermittent seizures may be overlooked when one is considering potential

etiologies. Both nonconvulsive status epilepticus and recurrent

focal or generalized seizures followed by postictal confusion can

cause delirium; EEG remains essential for this diagnosis and should

be considered whenever the etiology of delirium remains unclear

following initial workup. Seizure activity spreading from an electrical focus in a mass or infarct can explain global cognitive dysfunction caused by relatively small lesions.

It is extremely common for patients to experience delirium at the

end of life in palliative care settings. This condition must be identified and treated aggressively because it is an important cause of

patient and family discomfort at the end of life. It should be remembered that these patients also may be suffering from more common

etiologies of delirium such as systemic infection.

LABORATORY AND DIAGNOSTIC EVALUATION

A cost-effective approach allows the history and physical examination to guide further tests. No single algorithm will fit all delirious

patients due to the staggering number of potential etiologies, but

one stepwise approach is detailed in Table 27-3. If a clear precipitant such as an offending medication is identified, further testing

may not be required. If, however, no likely etiology is uncovered

with initial evaluation, an aggressive search for an underlying cause

should be initiated.

Basic screening labs, including a complete blood count, electrolyte panel, and tests of liver and renal function, should be obtained

in all patients with delirium. In elderly patients, screening for systemic infection, including chest radiography, urinalysis and culture,

and possibly blood cultures, is important. In younger individuals,

serum and urine drug and toxicology screening may be appropriate

earlier in the workup. Additional laboratory tests addressing other

autoimmune, endocrinologic, metabolic, and infectious etiologies

should be reserved for patients in whom the diagnosis remains

unclear after initial testing.

Multiple studies have demonstrated that brain imaging in patients

with delirium is often unhelpful. If, however, the initial workup is

unrevealing, most clinicians quickly move toward imaging of the

brain to exclude structural causes. A noncontrast computed tomography (CT) scan can identify large masses and hemorrhages but is

otherwise unlikely to help determine an etiology of delirium. The

ability of magnetic resonance imaging (MRI) to identify most acute

ischemic strokes as well as to provide neuroanatomic detail that

gives clues to possible infectious, inflammatory, neurodegenerative,

and neoplastic conditions makes it the test of choice. Because MRI

techniques are limited by availability, speed of imaging, patient’s

cooperation, and contraindications, many clinicians begin with CT

scanning and proceed to MRI if the etiology of delirium remains

elusive.

Lumbar puncture (LP) must be obtained immediately after

neuroimaging for all patients in whom CNS infection is suspected.

Spinal fluid examination can also be useful in identifying autoimmune, other inflammatory, and neoplastic conditions. As a result,

LP should be considered in any delirious patient with a negative

workup. EEG remains invaluable if seizures are considered or if

there is no cause readily identified.

paraneoplastic encephalitis; however, in light of the high morbidity

and mortality rates associated with these conditions when they

are not treated, clinicians must always maintain a high index of

suspicion.

In some susceptible individuals, exposure to the unfamiliar environment of a hospital itself can contribute to delirium. This etiology

usually occurs as part of a multifactorial delirium and should be

considered a diagnosis of exclusion after all other causes have been

thoroughly investigated. Many primary prevention and treatment

strategies for delirium involve relatively simple methods to address

the aspects of the inpatient setting that are most confusing.

182 PART 2 Cardinal Manifestations and Presentation of Diseases

TABLE 27-3 Stepwise Evaluation of a Patient with Delirium

Initial Evaluation

History with special attention to medications (including over-the-counter and

herbals)

General physical examination and neurologic examination

Complete blood count

Electrolyte panel including calcium, magnesium, phosphorus

Liver function tests, including albumin

Renal function tests

First-Tier Further Evaluation Guided by Initial Evaluation

Systemic infection screen

Urinalysis and culture

Chest radiograph

Blood cultures

Electrocardiogram

Arterial blood gas

Serum and/or urine toxicology screen (perform earlier in young persons)

Brain imaging with MRI with diffusion and gadolinium (preferred) or CT

Suspected CNS infection or other inflammatory disorder: lumbar puncture after

brain imaging

Suspected seizure-related etiology: electroencephalogram (EEG) (if high

suspicion, should be performed immediately)

Second-Tier Further Evaluation

Vitamin levels: B12, folate, thiamine

Endocrinologic laboratories: thyroid-stimulating hormone (TSH) and free T4

;

cortisol

Serum ammonia

Sedimentation rate

Autoimmune serologies: antinuclear antibodies (ANA), complement levels;

p-ANCA, c-ANCA, consider paraneoplastic/autoimmune encephalitis serologies

Infectious serologies: rapid plasmin reagin (RPR); fungal and viral serologies if

high suspicion; HIV antibody

Lumbar puncture (if not already performed)

Brain MRI with and without gadolinium (if not already performed)

Abbreviations: c-ANCA, cytoplasmic antineutrophil cytoplasmic antibody; CNS,

central nervous system; CT, computed tomography; MRI, magnetic resonance

imaging; p-ANCA, perinuclear antineutrophil cytoplasmic antibody.

TREATMENT

Delirium

Management of delirium begins with treatment of the underlying

inciting factor (e.g., patients with systemic infections should be

given appropriate antibiotics, and underlying electrolyte disturbances should be judiciously corrected). These treatments often

lead to prompt resolution of delirium. Blindly targeting the symptoms of delirium pharmacologically only serves to prolong the time

patients remain in the confused state and may mask important

diagnostic information.

Relatively simple methods of supportive care can be highly effective (Fig. 27-1). Reorientation by the nursing staff and family combined with visible clocks, calendars, and outside-facing windows

can reduce confusion. Sensory isolation should be prevented by

providing glasses and hearing aids to patients who need them.

Sundowning can be addressed to a large extent through vigilance

to appropriate sleep-wake cycles. During the day, a well-lit room

should be accompanied by activities or exercises to prevent napping. At night, a quiet, dark environment with limited interruptions by staff can assure proper rest; melatonin can be considered

before bed to promote sleep. These sleep-wake cycle interventions

are especially important in the ICU setting as the usual constant

24-h activity commonly provokes delirium. Attempting to mimic

the home environment as much as possible also has been shown

to help treat and even prevent delirium. Visits from friends and

FIGURE 27-1 Delirium management and prevention: a checklist for hospitalized

patients. Effective management of delirium relies on broad efforts to promote

wakefulness (A) and sleep (B). CPO, continuous pulse oximetry.

AM

Shades up. Lights on. Write date and staff

names on board to

orient patient.

Patient out of bed to

chair for all 3 meals.

Ask for assistance if

you need help.

Walk patient 3x/

day. Engage patient

in conversation.

Each visit, introduce

yourself; remind

patient where they

are, what day and

time it is.

Patient is wearing

hearing aids/glasses

(if needed) to hear

and see appropriately.

Hi, my name is...

Provide activities like

games and reading

materials to keep

patient’s mind active

while awake.

Make sure your

patient has water

within reach at all

times. Dehydration is

the #1 complaint in

the hospital!

Make sure family members have

been provided the pamphlet

about delirium and discuss any

questions they have. It is ok to

refer to the nurse or doctor if you

are unsure.

Discuss with the nurse at each

shift if the patient truly needs the

following: nasal cannula on their

nose, Foley catheter, telemetry,

and CPO. These “tethers” make

it difficult for the patient to move

and can contribute to confusion.

PROMOTE

WAKEFULNESS

PCA

RN

t t f b d

Delirium

Reduction Care

i i i

A

PM

Shades closed. Lights off. TV off. Make

room as dark and quiet as possible.

Group your nighttime tasks so that you

are entering the room and waking the

patient as few times as possible.

Discuss with the nurse each shift if they

need vital signs done overnight.

If you communicate with the patient during

the night, make sure glasses and hearing

aids are on. Remember to introduce

yourself, remind the patient where they are.

Minimize caffeine

intake.

PROMOTE

SLEEP

Offer eye mask, ear

plugs to help with

sleep.

Hi, my name is...

B

family throughout the day minimize the anxiety associated with

the constant flow of new faces of staff and physicians. Allowing

hospitalized patients to have access to home bedding, clothing, and

nightstand objects makes the hospital environment less foreign and

therefore less confusing. Simple standard nursing practices such as

maintaining proper nutrition and volume status as well as managing pain, incontinence, and skin breakdown also help alleviate

discomfort and resulting confusion.

In some instances, patients pose a threat to their own safety or

to the safety of staff members, and acute management is required.

Bed alarms and personal sitters are more effective and much less

disorienting than physical restraints. Chemical restraints should

be avoided, but when necessary, very-low-dose typical or atypical

antipsychotic medications administered on an as-needed basis can

be used, recognizing that clinical trials have consistently shown that

these medications are ineffective in treating delirium. Therefore,

they should be reserved for patients who display severe agitation

and significant potential to harm themselves or staff. The association of antipsychotic use in the elderly with increased mortality

rates underscores the importance of using these medications judiciously and only as a last resort. Benzodiazepines often worsen