Confusion

Daniel Press, MD, & Michael Ronthal, MD, BCh

Confusion is the inability to maintain a coherent stream of thought or action. Altered level of consciousness is
common in confusional states and can be the predecessor of stupor and coma if the underlying cause is not
found and reversed. Delirium refers to a confusional state caused by a medical condition. Patients with
delirium present a unique challenge in acquiring a history, because the organ system required to report on
symptoms, the central nervous system (CNS), is itself dysfunctional. For that reason, clinicians must obtain
most of the historical information from caregivers and family members. Nonetheless, the history is crucial to
determining the correct diagnosis. Often, delirium coexists with dementia.1 Demented patients are particularly
vulnerable to lapse into confusion, a state termed beclouded dementia. Among patients who present to an
emergency department with delirium, the diagnosis is overlooked in up to 40-60% of cases.2 Regardless of
cause, delirium confers a worse prognosis with higher hospital readmission rates and 30-day mortality,
especially if untreated.3 The causes of delirium differ greatly depending on the setting (ie, hospital versus
nonhospital).
KEY TERMS
Alertness

The level of arousal or responsiveness to external cues.

Attention

The ability to focus on specific stimuli and change from one

stimulus to another when salient.

Confusion

Inability to maintain a coherent stream of thought.

Delirium

Acute impairment in attention with fluctuating course and

altered level of consciousness caused by a medical condition;
also called acute confusional state and encephalopathy.

Dementia

Chronic degenerative condition affecting memory, behavior,

and cognition.

ETIOLOGY
The cause of delirium differ for persons in the community and those hospitalized for a medical illness. In the
hospital setting, delirium generally occurs in patients with predisposing risk factors (see below).4 While sever
illnesses, large doses of CNS-active medications, and severe metabolic impairments can cause delirium even in
low risk patients, a relatively mild insult can trigger it in patients with multiple risk factors. Causes of delirium
in the community can be subdivided into 3 large categories: primary insults to the CNS (seizures, stroke, or
meningitis), systemic metabolic conditions impairing CNS function (systemic infections, hypoxia, hypotension,
renal failure, or hepatic failure), or the effect of medications (see Differential Diagnosis below).
Risk factors

Relative risk

Use of physical restraints

4.4 (2.5-7.9)

Malnutrition

4.0 (2.2-7.4)

> 3 medications added during hospital stay

2.9 (1.6-5.4)

Use of bladder catheter

2.4 (1.2-4.7)

Any iatrogenic event

1.9 (1.1-3.2)

Differential Diagnosisa

Prevalenceb

Primary CNS causes

35%

Meningitis/encephalitis
Stroke (primarily right hemisphere, either frontal, parietal,
or occipital lobes)
Seizures (postictal state or partial seizures)
Head trauma
Secondary CNS causes

60%

Infections, especially urinary tract infection (UTI),

pneumonia, or sepsis

5%

Hypoxia

25%

Hypoperfusion (eg, congestive heart failure, shock)

5%

Hypoglycemia

5%

Renal failure

5%

Hepatic failure
Toxins (carbon monoxide, heavy metals)
Medications

5%

Alcohol (intoxication or withdrawal)

3%

Narcotic analgesics
Opiates
Amphetamines
Anticholinergic drugs (especially didphenhydramine)
Drug withdrawal syndromes
a

Causes of delirium among elderly patients presenting to emergency departments.2

Prevalence is unknown when not indicated.

GETTING STARTED
The confused patient often cannot provide a coherent history. Ask focused questions regarding the
presence of headache, recent drug use, and fevers.
Confirm the history with a caregiver. Make every effort to contact a caregiver if no one is with the
patient. This crucial task may require some detective work.

Always determine the patients current medications and whether any have changed. An accurate
determination often requires calls to the patients pharmacy or requests to have the family bring in all
the medication bottles.
In young patients, consider both the acute effects of drugs of abuse and withdrawal states.

INTERVIEW FRAMEWORK
The goal is to determine the acute cause of the confusion and establish the presence of any baseline risk
factors (eg, dementia, malnutrition).
Inquire about timing of the episode
o Previous episodes?
o Suddenness of onset?
o Any baseline confusion?
Associated symptoms
o Fever?
o Shortness of breath?
o Headache?
o Abnormal motor activity?
Drug usage
o Any recent change in drug regimen?
o Use of drugs of abuse or pain medications?
o Recent drug withdrawal?
IDENTIFYING ALARM SYMPTOMS
Delirium itself usually reflects serious CNS dysfunction, especially if the onset has been acute. Delirium is a
common presentation of life-threatening conditions, including subarachnoid hemorrhage, meningitis, and
increased intracranial pressure due to a mass lesion. A number of investigations are often necessary to
determine the cause; certain symptoms will suggest which tests should be done first.
Alarm symptoms

Serious causes

Benign causes

Fever or hypothermia

Meningitis
Sepsis

UTI
Upper respiratory tract infection
(URI)

Abnormal motor activity or history of

epilepsy

Seizures (status epilepticus) or

postictal state

Myoclonus or asterixis from

metabolic disturbance

Headache

Stroke
Meningitis
Mass lesion

Migraine and confusion due to

excess pain medication

Shortness of breath

Hypoxia (congestive heart failure,

pneumonia)

URI

Diaphoresis, tremors

Hypoglycemia

Fever

Neglect (inattention to 1 side of

space) or visual field loss

Stroke

Glaucoma
Macular degeneration

Ataxia, nystagmus

Wernicke encephalopathy

Alcohol or drug intoxication

FOCUSED QUESTIONS
Questions

Think about

Do you have

History of seizures?

Postictal state
Nonconvulsive status epilepticus

Pain on urination or recent urinary catheter?

UTI
Urosepsis

Shortness of breath?

Congestive heart failure

Pneumonia
Pulmonary embolism in postoperative patient

History of insulin-requiring diabetes?

Hypoglycemia

History of liver problems?

Hepatic encephalopathy

Headache?

Meningitis
Stroke
Subarachnoid hemorrhage

Have you recently used sleep medications?

Anticholinergic or sedative toxicity

Have you fallen recently?

Unwitnessed head trauma

Have you experienced memory problems

previously?

Underlying dementia

Quality

Think about

Is the confusion primarily a memory problem?

Dementia

Or does the patient have poor attention, especially

with fluctuations?

Delirium

Time Course

Think about

Is the onset

Sudden (over seconds)?

Seizure
Stroke
Subarachnoid hemorrhage

Over minutes to hours?

Drug-induced
Hypoxia
Hypoglycemia

Over hours to days?

Infection
Renal failure
Hepatic failure

Gradual progression over months?

Dementia

Associated symptoms

Think about

Do you have

Altered level of consciousness?

Delirium of any cause

Hypervigilence?

Drug or alcohol withdrawal

Wernicke encephalopathy

Shortness of breath?

Congestive hart failure

Myocardial infarction
Pulmonary embolism

Headache?

Subarachnoid hemorrhage
Mass lesion
Meningitis

Blurred vision? (monocular)

Cavernous sinus disease

Pituitary apoplexy

Blurred vision? (binocular)

Parietal or occipital lobe stroke or mass lesion

Hypertensive encephalopathy

Stiff neck?

Meningitis (bacterial, viral, neoplastic, or aseptic)

Vertigo?

Cerebellar or brainstem lesion

Jaundice?

Hepatic encephalopathy

Dysuria or anuria?

UTI
Pyelonephritis
Uremic encephalopathy

Modifying factors

Think about

Are symptoms worse at nighttime?

Sundowning (may be due to delirium or underlying

dementia)

Is there rapid improvement over seconds?

Postsyncope (see Chapter 26)

Is there rapid improvement over minutes to hours?

Postictal state

Are symptoms worse when standing?

Hypoperfusion

History of seizures?

Nonconvulsive status epilepticus

Ask both patient and caregiver.

DIAGNOSTIC APPROACH
The diagnostic approach to confusion depends on 3 factors: the temporal course, the presence of focal
neurologic signs, and the age of the patient. An acute onset over hours to days suggest delirium, while a gradual
onset over months suggest underlying dementia. If the onset is acute, rapidly search for an underlying
reversible cause that may be life-threatening without treatment. Focal symptoms (visual changes, headache,
focal weakness or numbness) suggest a primary CNS process. The central causes include CNS infections

(meningitis, abscess), strokes (ischemic or hemorrhagic), mass lesions (tumors), or seizures (with postictal
state). If delirium develops without focal signs or symptoms, the patients age may help determine the likely
cause.
In younger patient without a focal CNS cause, drug use or withdrawal, unwitnessed head trauma, and
unwitnessed seizure should be considered. When delirium develops in the elderly, likely causes include
systemic infections (UTI, pneumonia), drugs (especially opiates and anticholinergic medications), hypoxia,
hypoperfusion, and metabolic disturbances (renal failure, hepatic failure). In hospitalized patients, questions
should focus both on the cause of the delirium and predisposing risk factors (see above).
A number of concomitant medical conditions bring up special concerns.

Epilepsy: Confusion is most often due to postictal state, but a sudden worsening in confusion or
fluctuating course suggests ongoing seizures or nonconvulsive status epilepticus.
Diabetes: Both hypoglycemia and hyperglycemia (with either acidosis or a hyperosmolar state) can
present as confusion. In patients with diabetes, confusion can also develop from either cerebral
ischemia (stroke) or coronary ischemia (myocardial infarction).
Hepatic cirrhosis: Confusion can be a sign of worsening cirrhosis but may also herald upper
gastrointestinal bleeding from varices (causing cerebral hypoperfusion or hepatic encephalopathy).
Drug-induced delirium is also more common due to impaired hepatic metabolism.
Parkinsons disease: In addition to the usual causes, anticholinergic drugs and dopamine agonists can
cause confusion.
Cancer: Cancer may cause confusion via direct cerebral mechanisms (metastases, carcinomatous
meningitis), indirect mechanisms (drug effects, paraneoplastic states), and systemic mechanisms
(Hypercalcemia, hyponatremia, hepatic encephalopathy due to liver metastases, uremic encephalopathy
due to obstructive uropathy).
HIV/AIDS: HIV can predispose to confusion through CNS infections (toxoplasmosis, cryptococcal
meningitis, progressive multifocal leukoencephalopathy) as well as directly (HIV dementia).
Complicated treatment regimens with large numbers of medications can also predispose to confusion.
Postoperative patients: If confusion is present immediately upon awakening from surgery, consider an
intraoperative event (eg, global hypoxia/hypoperfusion or a focal stroke). In days 1-3 after surgery,
hypoxia (from pneumonia or a pulmonary embolism) and drug withdrawal should be considered in
addition to other causes of confusion in hospitalized patients.

CAVEATS
The confused patients ability to communicate and provide useful history can fluctuate markedly. Be
sure to get ancillary information from other caregivers and, when in doubt, evaluate the patient at
different times.
Do not assume that confusion has been longstanding in a patient who appears demented. Err on the
side of assuming there is a treatable delirium present, even in patients with chronic cognitive deficits.
Delirium and dementia often coexist. Determining whether an underlying dementia is present is nearly
impossible in the setting of a delirium. Appropriate testing and interventions should be planned after the
causes of the confusion have been treated.
PROGNOSIS
Some symptoms of delirium can persist for 6 months or longer in up to 80% of patients.5 Those persons in who
delirium develops during a hospital stay are much more likely to require long-term intuitional care; 43% reside
in an institution at 6 months. The 1-month mortality for hospitalized patients with delirium is approximately
14% and is significantly higher than controls even when accounting for comorbid conditions.6 Mortality for
those with delirium is 39% at 1 year, roughly twice the likelihood compared with age-matched controls.4 While
delirium is frequently completely reversible, it is often the harbinger of more serious and chronic cognitive
defects.

REFERENCES
1) Rahkonen TR, Luukkainen-Markkula R, Pannila S, et al. Delirium episode as a sign of undetected
dementia among community dwelling elderly subjects: a 2 year follow up study. J Neurol Neurosurg
Psychiatry. 2000;69:519-521.
2) Lewis LM, Miller D, Morley JE, et al. Unrecognized delirium in ED geriatric patients. Am J Emerg
Med. 1995;13:142-145.
3) Francis J, Kapoor WN. Prognosis after hospital discharge of older medical patients with delirium. J Am
Geriatr Soc. 1992;40:601-606.
4) Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive
model and interrelationship with baseline vulnerability. JAMA. 1996;275:852-857.
5) Francis J, Martin D, Kappor WN. A prospective study of delirium in hospitalized elderly. JAMA.
1990;263:1097-1101.
6) Cole MG, Primeau FJ. Prognosis of delirium in elderly hospital patients. CMAJ. 1993;149:41-46.
SUGGESTED READING
American Psychiatric Association. Delirium: Practice Treatment Guideline. 1998. Available at
http://www.psych.org/psych_pract/treatg/pg/pg_delirium_1.cfm
Brown TM, Boyle MF. Delirium. BMJ. 2002;325:644-647.
Francis J. Recognition and evaluation of delirium. 2003. UpToDate. B. Rose. Wellesley, MA. Available at
http://www.uptodate.com

Diagnostic Approach: Confusion

Confusion

Duration of
symptoms

Hours to days

Weeks to months

Delirium

Superimposed
delirium

Focal CNS symptoms

(headache, field cut,
neglect, abnormal
motor activity)?

Yes

Meningitis
Drug use/withdrawal
Head trauma
Epilepsy
HIV-related illness

Focal CNS
symptoms
(headache, field
t
l t

Yes

No

Stroke
Seizure
Trauma
CNS bleed
Mass lesion

Dementia

Recent
exacerbation?

See Chapter 55
(Memory Loss)

Infections (meningitis, UTI, pneumonia)

Metabolic cause (hypoxia, hypoperfusion, renal
failure, hepatic failure)
Drugs (pain medications, anticholinergics)

CNS, central nervous system; UTI, urinary tract

infection; HIV, human immunodeficiency virus