Chapter 9

An Approach to Acute Changes

JOHN QUERQUES, MD
in Mental Status

A. Acute Mental Status Changes

I. Overview

An acute change in mental status is any alteration of affect,

behavior, or cognition that develops over hours to days. Any ele-
ment of a standard mental status examination (MSE) can be affect-
ed: alertness, attention, concentration, memory, orientation, compre-
hension, constructional ability, language, mood, thought process,
thought content, or perception. Impairment of several domains at
once is the rule.

B. Syndromes Manifest by Mental Status Changes

Delirium is but one syndrome manifest by an alteration in con-
sciousness and cognition (Table 9-1). Other terms that are general-
ly considered synonymous with delirium (though some authors
argue their distinctions) are acute confusional state, acute confu-
sion, and encephalopathy.

C. Psychosis
Psychosis is a syndrome of altered thinking, perception, and be-
havior that severely impairs the patient’s ability to understand
and experience reality; however, it spares consciousness. Its hall-
mark features are delusions (i.e., fixed, false beliefs not shared by
other members of the patient’s sociocultural group) and hallucina-
tions (i.e., false perceptions in any of the five sensory modalities).

D. Consciousness
Delirium and psychosis share certain features (Figure 9-1).
Agitation, delusions, hallucinations, illusions, and disorders of thought
process (e.g., loose associations and circumstantiality) are common to
both conditions. Despite this overlap, however, the two syndromes
are distinct. The differential diagnosis is aided by a simple dichoto-
mous determination: consciousness is always normal in “function-
al” psychosis and is always abnormal in delirium. Moreover, save

97
98 Ten-Minute Guide to Psychiatric Diagnosis and Treatment

• Disturbance of consciousness with diminished ability to focus, sustain,

Table 9-1. DSM-IV Criteria for Delirium

or shift attention
• Change in cognition or new-onset perceptual disturbance not due to
dementia
• Acute development (usually over hours to days) of these alterations
with fluctuation during the day
• Historical, physical, or laboratory evidence that these alterations have
a medical etiology
Adapted from: American Psychiatric Association: Diagnostic and Statistical
Manual of Mental Disorders, 4th edition. Washington, DC: American
Psychiatric Association, 1994.

for psychosis that develops as a result of intoxication (e.g., cocaine

or phencyclidine), most cases of functional psychosis develop insid-
iously over weeks to months. For these reasons, the often-invoked
term “intensive care unit (ICU) psychosis” is a regrettable mis-
nomer applied to critically ill patients in ICUs who develop acute
mental status changes. Delirium, not psychosis, is the usual cause of

DELIRIUM PSYCHOSIS

Agitation
Abnormal Delusions Normal
sensorium sensorium
Hallucinations
Fluctuating Steady
Illusions course
course
Abnormal
thought
processes

Figure 9-1. Relationship between Delirium and

Psychosis
Chapter 9 • An Approach to Acute Changes in Mental Status 99

such disturbances, and the causative role of the ICU environment is

much less important etiologically than are the nature, severity, and
number of the patient’s medical morbidities.

A. Epidemiology
II. Delirium

Delirium is most common in patients with advanced age; brain im-

pairment (e.g., stroke, dementia, or traumatic brain injury); recent
surgery; multiple medical problems, particularly if they are active;
extensive medication regimens; a history of delirium; sensory depri-
vation or overload; impaired vision or hearing; and experience of a
recent change in surroundings (e.g., associated with hospitalization).
Often, more than one of these risk factors for the development of
delirium is present at the same time. Because of its profound effects
on levels of arousal and attention, delirium is more commonly diag-
nosed in medical settings (e.g., medical and surgical units or emer-
gency departments) than in psychiatric venues.

B. Prevalence
Estimates of the prevalence of delirium vary according to the popu-
lation studied. Among hospitalized medical patients, the prevalence
of delirium is roughly 10–30%. Higher prevalence figures are usu-
ally reported in the elderly and in patients following surgery.

C. Etiology
Many roads lead to delirium. The mnemonic WWHHHHIIMP (Table
9-2) summarizes the life-threatening causes of delirium that need to be
ruled out first. A more comprehensive list of possible etiologies can be
divided into the 11 categories recalled by the mnemonic I WATCH
DEATH (Table 9-3). Frequently more than one etiology is respon-
sible for the delirious state and a combination of minor abnormali-
ties may contribute to alterations in mentation (i.e., the whole is
greater than the sum of its parts).

D. Mechanism
The pathogenic links between these multifarious etiologies and the
ultimate production of delirium are largely unknown. However, con-
sideration of the “wires” (neuroanatomy) and the “juices” (neuro-
chemistry) may yield putative answers. Alertness is mediated by
the ascending reticular activating system (RAS) and its thalamic
projections to both hemispheres; attention is mediated by neocor-
tical and limbic inputs to this system. Any structural alteration of
these neural fibers theoretically could result in delirium. Moreover,
100 Ten-Minute Guide to Psychiatric Diagnosis and Treatment

Table 9-2. Life-Threatening Causes of Delirium:

Withdrawal
WWHHHHIIMP

Wernicke’s encephalopathy
Hypertensive encephalopathy
Hypoglycemia
Hypoxia
Hypotension/hypoperfusion
Intracranial hemorrhage
Infection
Meningitis/encephalitis
Poisoning
Adapted from: Wise MG, Trzepacz PT: Delirium (confusional states). In
Rundell JR, Wise MG (eds): The American Psychiatric Press Textbook of
Consultation-Liaison Psychiatry. Washington, DC: American Psychiatric
Press, 1996:258–274.

because the RAS is a cholinergic system, a deficit in acetylcholine

could render this critical arousal network defunct. This anatom-
ical and chemical hypothesis is consistent with the clinical recogni-
tion of anticholinergic deliria. Overdose of any agent that has signif-
icant anticholinergic properties (e.g., tricyclic antidepressants [TCAs],
diphenhydramine, and some neuroleptics) are frequent causes of
anticholinergic delirium. A complementary theory posits that deliri-
um is a hyperdopaminergic state. Support for this contention comes
from research evidence that stress (e.g., that which ensues postoper-
atively) stimulates dopamine output in the mesocorticolimbic tract.
This hypothesis coincides squarely with the overwhelming success
of dopamine-blocking drugs in the treatment of delirium.

E. History
To gather useful history from the delirious patient, the examiner
must be fortunate enough to “catch him on the wane,” that is, when
he is more lucid and coherent. Even then, however, the information
he provides may be of dubious reliability and the clinician may have
to rely on collateral sources of information. Whether from the
patient or from these ancillary informants, the crucial questions to
ask are:
Chapter 9 • An Approach to Acute Changes in Mental Status 101

Table 9-3. Differential Diagnosis of Delirium:

Infection Any, but especially meningitis, encephalitis, bac-

I WATCH DEATH

teremia, tertiary syphilis, human immunodeficiency

virus (HIV) infection, and urinary tract infection
(UTI) in elderly patients
Withdrawal Alcohol, benzodiazepines, or barbiturates
Acute metabolic Electrolyte derangements, fluid imbalances, renal fail-
ure, hepatic failure, or acid-base disorder
Trauma Head injury, burns, or fractures
CNS pathology Any
Hypoxia Anemia, hypotension, hypoperfusion, heart failure,
respiratory failure, or carbon monoxide poisoning
Deficiencies Vitamin B12 (cyanocobalamin), folate, or thiamine
Endocrinopathies Dysfunction (increase or decrease of activity) of pitu-
itary, thyroid, and adrenal glands; hyperglycemia; or
hypoglycemia
Acute vascular Emergent or urgent hypertension, stroke, shock, or
myocardial infarction
Toxins/drugs Any toxin; see also Table 9-4
Heavy metals Lead, manganese, or mercury
Adapted from: Wise MG, Trzepacz PT: Delirium (confusional states). In
Rundell JR, Wise MG (eds): The American Psychiatric Press Textbook of
Consultation-Liaison Psychiatry. Washington, DC: American Psychiatric
Press, 1996:258–274.

1. What is the patient’s baseline level of function? This deter-

mination helps ascertain the extent and nature of the deviation
from the patient’s usual affective, behavioral, and cognitive
state.
2. What are the patient’s medical problems? In addition to
inquiries related to the conditions listed in Tables 9-2 and 9-3,
specific queries about any brain insults—both remote and
recent—should be made. Any brain insult heightens vulnerabil-
ity to delirium. Moreover, recent head injury, seizure, or stroke
may point to an emergent intracranial catastrophe. Brain insults
include:
a. Head injury
102 Ten-Minute Guide to Psychiatric Diagnosis and Treatment

b. A fall that may have resulted in an occult head injury

c. Seizure
d. Stroke
e. Human immunodeficiency virus (HIV) infection
f. Dementia
3. What medications does the patient take? Were any recently
started or discontinued? A variety of medications have been
associated with delirium (Table 9-4). Pharmaceuticals recently
added to the patient’s regimen can be especially significant, as
these would be more likely to cause a mental status change,
either by pharmacodynamic or pharmacokinetic means. Fre-
quently overlooked are drugs newly removed from the patient’s
drug regimen. Withdrawal from certain medications (e.g., benzo-
diazepines, opiates, or barbiturates) can lead to delirium. More-
over, when cytochrome P450 inducers (e.g., carbamazepine, ste-
roids, or tobacco [of particular relevance in hospitalized patients
who may be barred from smoking]) are stopped, levels of drugs
(e.g., benzodiazepines, cyclosporine, or clozapine) metabolized
through this pathway may increase in serum level. When P450
inhibitors (e.g., azole antifungals, or selective serotonin reup-
take inhibitors) are discontinued, levels of remaining drugs
(e.g., benzodiazepines or TCAs) may decrease. Either of these
alterations in the patient’s medication regimen can precipitate
mental status changes.
4. Does the patient abuse alcohol or other drugs? Has he
recently stopped using these substances? Intoxication and
abrupt withdrawal are frequent causes of delirium. Intoxication
with ethanol substitutes (e.g., ethylene glycol or methanol)
should also be considered, as these compounds may be exploit-
ed for their inebriating properties or to effect suicide.

F. Physical Examination
A general physical examination, targeting the physical findings ex-
pected in the conditions listed in Tables 9-2 and 9-3, is critical to the
prompt and proper identification of the etiology of delirium. Such an
evaluation has typically been completed before the psychiatrist is
called to assess the patient. The psychiatrist’s contribution is per-
formance of a comprehensive MSE, which is no different from that
discussed in Chapter 3. A few key points about the evaluation of the
delirious patient warrant elaboration.
1. Observation
Much critical data can be gleaned by simply observing the
patient. While perusing the record, the clever examiner gathers
much useful information by keeping the patient in his visual
Chapter 9 • An Approach to Acute Changes in Mental Status 103

Table 9-4. Some Medications and Medication Classes

Analgesics Antineoplastics
Associated with Delirium

Corticosteroids Asparaginase
Nonsteroidal anti-inflammatory Cytarabine
drugs Ifosfamide
Salicylates Interleukin-2
Antiepileptics Antiparkinsonians
Antimicrobials Levodopa
Acyclovir Selegiline
Chloroquine Cardiac medications
Efavirenz Acetazolamide
Fluoroquinolones Beta-adrenergic blockers
Ganciclovir Calcium channel blockers
Mefloquine Digoxin
Metronidazole Propafenone
Nevirapine Quinidine
Sulfonamides Histamine (H2-receptor)
blockers
Miscellaneous
Baclofen
Pilocarpine
Sildenafil
Adapted from: Drugs that may cause psychiatric symptoms. Med Lett Drugs
Ther 2002;44:59–62.

field and noting: coarse motor activity (e.g., picking at the

sheets, thrashing, or near stillness); verbal output (e.g., loud or
vulgar utterances); and cooperation with staff. Before greeting
the patient or otherwise attracting his notice, the examiner
should observe him more closely and note, in addition to the
above: general appearance (does the patient look comfortable
in the bed?; are the sheets and blankets in disarray?); fine motor
activity (e.g., tremor, myoclonus, or adventitious orobuccal
movements); skin (e.g., diaphoretic, dry, or red); and pupils
(e.g., mydriasis or miosis). Only then does the clinician greet the
patient and note his response: Does he turn toward the examin-
er? Does he make eye contact? Does he track as the examiner
walks farther into the room? Does he greet the clinician in
104 Ten-Minute Guide to Psychiatric Diagnosis and Treatment

return? Note that even in a heavily sedated intubated patient, all

of these observations are still possible.
Levels of alertness and attentiveness must be assessed first
because the remainder of the examination requires that the pa-
tient’s full attention be focused on the prescribed questions and
tasks. Patients who lack full alertness can be assessed using the
Glasgow Coma Scale (Table 9-5), which assesses eye opening,
verbal output, and motor activity, and rates alertness on a scale
from 3 to 15. Additionally, a narrative comment about the pa-
tient’s response to various stimuli should be documented. For
example: The patient’s eyes were closed on approach and did
not open upon verbal stimulus, nor did they open with vigorous
shaking of his shoulder. Only when sternal pressure was applied
did his eyes open—and even then only for a second—and he
mumbled a few incomprehensible sounds. Such a description
clearly communicates the patient’s status, which can then be ea-
sily compared to subsequent observations.
Attention refers to the ability to focus awareness on a
particular stimulus and to exclude all competing stimuli. The
patient who focuses on all manner of stimuli (e.g., the examin-

Category Response Points

Table 9-5. Glasgow Coma Scale

Eye opening Spontaneous 4

To verbal command 3
To pain 2
None 1
Best verbal output Oriented, converses 5
Disoriented, converses 4
Inappropriate words 3
Incomprehensible sounds 2
None 1
Best motor output Obeys command 6
Localizes pain 5
Withdraws from pain 4
Abnormal flexion (decorticate) 3
Abnormal extension (decerebrate) 2
None 1
Adapted from: Teasdale G, Jennett B: Assessment of coma and impaired
consciousness, a practical scale. Lancet 1974;2:81–84.
Chapter 9 • An Approach to Acute Changes in Mental Status 105

er, the nurse walking by the door, or the soft whir of the intra-
venous pump) can be described as distractible, hyperalert, and
inattentive. More subtle cases of inattention can be identified by
specific tests (e.g., digit span).

G. Laboratory Assessment
A routine work-up for delirium includes: a complete blood count
(CBC), comprehensive chemistries, levels of vitamin B12 and folate,
a rapid plasma reagin (RPR) test, urinalysis (U/A), chest radiograph
(CXR), and electrocardiogram (ECG). Thyroid-stimulating hor-
mone (TSH) is also commonly ordered as part of a general screen,
but it is frequently abnormal in a critically ill patient, even one with-
out intrinsic thyroid disease, rendering its utility questionable. The
need for additional diagnostic testing is dictated by the history, the
physical examination, the initial laboratory test results, and the pa-
tient’s response to treatment. These supplementary procedures often
include: computed tomography (CT) of the head, magnetic reso-
nance imaging (MRI) of the brain, electroencephalogram (EEG), ce-
rebrospinal fluid (CSF) analysis, and cultures of various fluids.

H. Pharmacological Treatment
The definitive therapy for delirium is treatment of its underly-
ing cause(s); it is usually left to the ministrations of medical and
surgical personnel. If the patient’s affective, behavioral, or cognitive
disturbance is severe enough to put him or others at risk, additional
treatment with a neuroleptic medication is indicated. For example, a
delirious patient with a persecutory delusion that the medical and
nursing staff are trying to harm him may refuse necessary diagnos-
tic tests and therapeutic interventions. He may even disconnect him-
self from various monitors, remove catheters, and attempt to leave
the hospital prematurely. Some clinicians argue that delirium per se
is neurotoxic, and even in the absence of such florid derangements
prescribe a neuroleptic medication.
1. Based on decades of clinical experience, haloperidol is the
treatment of choice for the adjunctive therapy of delirium.
For acute or florid agitation, haloperidol should be administered
intravenously (though this route is not approved by the U.S.
Food and Drug Administration), starting with a dose of 1–5 mg,
which is successively doubled every 30 minutes until agitation
resolves. Once calm, the patient can be maintained on an intra-
venous (IV) haloperidol drip, or more commonly on a standing
regimen of IV or oral haloperidol. For less severe agitation,
haloperidol can be administered orally; a typical starting dose is
1–5 mg two or three times a day.
106 Ten-Minute Guide to Psychiatric Diagnosis and Treatment

2. With the burgeoning popularity of the atypical antipsychotic

agents, these pharmaceuticals are increasingly being used for
treatment of delirium. Some small studies have shown them to
be safe and effective.

I. Psychological Treatment
Frequent reassurance, explanation of the patient’s circumstan-
ces, and orientation to time and place should be provided to the
patient in clear, simple language, especially during more lucid
phases of the delirium. He should be approached and spoken to with
the assumption that he registers some measure of external reality, in
much the same way a comatose patient may be treated. Once the
delirium has resolved, a brief explanation of the episode should be
offered and the patient permitted to talk about his or her experience.
Throughout the encounter, the psychiatrist should be available to the
patient’s visitors and caretakers to explain delirium, to answer ques-
tions, and to provide support, as the experience of delirium can be
frightening to the patient and to those around him or her.

J. Behavioral Treatment
Acute and florid agitation often requires application of soft or leather
restraints of two, three, or all limbs. When two limbs are restrained,
one arm and the contralateral leg should be selected, as other com-
binations are more dangerous to the patient. Concomitant treatment
with a sedating medication is almost always in order when restrain-
ing patients, as the discomforting experience of physical restraint is
akin to that of pharmacological paralysis. Soft vests around the
patient’s torso prevent thrashing about in the bed and the attendant
risk of injury (e.g., by dislodging vital medical equipment, incurring
blunt force trauma, or falling out of bed). Hand mitts can be used to
hamper the patient’s attempts to remove various catheters and wires.
The patient who wanders or whose agitation or confusion may be
quelled simply by the presence of another person often benefits from
constant observation.

Psychosis shares a variety of features with delirium. However, functional

III. Acute Psychosis

psychosis always occurs within a clear sensorium (i.e., the patient is fully
awake, alert, and attentive), whereas by definition delirium involves a be-
clouding of consciousness. In a general medical setting, the development of
psychotic symptoms over hours to days is rare and should always raise sus-
picion of delirium; an assessment of the patient’s levels of alertness and
Chapter 9 • An Approach to Acute Changes in Mental Status 107

attention should be made urgently. Once delirium has been excluded, atten-
tion should focus on illicit drug use and withdrawal phenomena.

Suggested Readings
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Dis-
orders, 4th edition. Washington, DC: American Psychiatric Association, 1994.
Burns A, Gallagley A, Byrne J: Delirium. J Neurol Neurosurg Psychiatry 2004;75:
362–367.
Crippen DW: Pharmacologic treatment of brain failure and delirium. Crit Care Clin
1994;10:733–766.
Drugs that may cause psychiatric symptoms. Med Lett Drugs Ther 2002;44:59–62.
Gleason OC: Delirium. Am Fam Physician 2003;67:1027–1034.
Meagher DJ: Delirium: optimising management. BMJ 2001;322:144–149.
Misra S, Ganzini L: Delirium, depression, and anxiety. Crit Care Clin 2003;19:
771–787.
Practice guideline for the treatment of patients with delirium. Am J Psychiatry 1999;
156(5 Suppl):1–20.
Strub RL, Black FW: The Mental Status Examination in Neurology, 3rd edition.
Philadelphia: F. A. Davis, 1993.
Teasdale G, Jennett B: Assessment of coma and impaired consciousness, a practical
scale. Lancet 1974;2:81–84.
Wise MG, Trzepacz PT: Delirium (confusional states). In Rundell JR, Wise MG
(eds): The American Psychiatric Press Textbook of Consultation-Liaison Psy-
chiatry. Washington, DC: American Psychiatric Press, 1996:258–274.