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Am Fam Physician. 2021;104(5):461-470

Author disclosure: No relevant financial affiliations.

Potential precipitating factors for the recent onset of altered mental status (AMS) include primary central nervous system insults, systemic infections, metabolic disturbances, toxin exposure, medications, chronic systemic diseases, and psychiatric conditions. Delirium is also an important manifestation of AMS, especially in older people who are hospitalized. Clinicians should identify and treat reversible causes of the AMS, some of which require urgent intervention to minimize morbidity and mortality. A history and physical examination guide diagnostic testing. Laboratory testing, chest radiography, and electrocardiography help diagnose infections, metabolic disturbances, toxins, and systemic conditions. Neuroimaging with computed tomography or magnetic resonance imaging should be performed when the initial evaluation does not identify a cause or raises concern for intracranial pathology. Lumbar puncture and electroencephalography are also important diagnostic tests in the evaluation of AMS. Patients at increased risk of AMS benefit from preventive measures. The underlying etiology determines the definitive treatment. When intervention is needed to control patient behaviors that threaten themselves or others, nonpharmacologic interventions are preferred to medications. Physical restraints should rarely be used and only for the shortest time possible. Medications should be used only when nonpharmacologic treatments are ineffective.

Altered mental status (AMS) can present as changes in consciousness, appearance, behavior, mood, affect, motor activity, or cognitive function.13 Recent changes are the focus of this article and are approached differently than chronic changes. Recent changes occur within seconds to days and usually pose a more immediate threat to a patient's well-being than chronic changes.24

Clinical recommendation Evidence rating Comments
Delirium is common but frequently overlooked, and it is associated with serious medical conditions; therefore, screening should always be considered in patients with acute AMS, especially in those at high risk.6,9,11 C Systematic review, narrative review, and expert consensus
Unless the etiology is clear and the risk of intracranial pathology is low, neuroimaging should be part of the initial assessment of recent changes in mental status. Noncontrast computed tomography of the head is the initial study for most patients.1214 C Expert consensus
Electroencephalography is an important study to rule out nonconvulsive seizures, which may occur in 8% to 30% of patients with AMS without an obvious cause.16 C Evidence-based review
 
When patients are at risk of AMS or delirium, nonpharmacologic preventive measures decrease incidence, especially in those who are hospitalized. The use of multiple measures through a multidisciplinary team approach is most effective.6,9,11 B Systematic review, narrative reviews, and expert consensus
Medication to manage behaviors associated with AMS should be used only when nonpharmacologic measures are ineffective, and then only when it is essential to control behavior. Studies evaluating the effectiveness of medications used for their sedative effects yield conflicting results, and these medications may cause harm due to adverse effects.11,23,24 C Systematic reviews, cohort study, and expert consensus
RecommendationSponsoring organization
Do not assume a diagnosis of dementia in an older adult who presents with an altered mental status and/or symptoms of confusion without assessing for delirium or delirium superimposed on dementia using a brief, sensitive, validated assessment tool.American Academy of Nursing
Do not use antipsychotics as the first choice to treat behavioral and psychological symptoms of dementia.American Geriatrics Society
Do not use physical or chemical restraints, outside of emergency situations, when caring for long-term care residents with dementia who display behavioral and psychological symptoms of distress; instead, assess for unmet needs or environmental triggers and intervene using nonpharmacologic approaches initially whenever possible.American Academy of Nursing

AMS is common and is estimated to account for 5% of adult emergency department encounters.5 Older people are especially susceptible, as evidenced by their high rates of delirium (Table 1).6 Additionally, AMS is associated with poor patient outcomes, especially when recognition is delayed.7,8

SettingRate
Incidence during hospital admission
After hip fracture28% to 61%
After surgery15% to 53%
During hospitalization (medical inpatients)3% to 29%
Prevalence
Intensive care unit
 With mechanical ventilation60% to 80%
 Without mechanical ventilation20% to 50%
Hospice29%
Community (people 85 years or older)14%
At hospital admission10% to 31%
Long-term care facility and postacute care1% to 60%

The differential diagnosis for AMS is broad. A history and physical examination are the cornerstones of diagnosis, and their findings guide diagnostic testing. Preventive measures can decrease incidence and are important to use in patients at high risk. The goal of treatment is to correct the precipitating cause of the AMS.2,3,911

Causes of Recent AMS

Causes of recent AMS include primary central nervous system insults, systemic infections, metabolic disturbances, toxin exposure, medications, chronic systemic diseases, and psychiatric conditions (Table 2).24,9,10 Although a single abnormality may cause the alteration in mental status (e.g., opiate overdose), often the cause is multifactorial (e.g., dehydration, constipation, high-risk medication use).24,9,10

Central nervous system insults
Demyelinating conditions
Direct brain trauma (concussion)
Epidural hematoma
Intraparenchymal hemorrhage
Ischemic stroke
Meningoencephalitis
Neoplasm (primary or metastatic)
Seizure (status epilepticus, nonconvulsive status epilepticus, or postictal state)
Subarachnoid hemorrhage
Subdural hematoma
Commonly used medications
Antibiotics (fluoroquinolones, cephalosporins)
Antidepressants (tertiary amine tricyclics, monoamine oxidase inhibitors)
Antipsychotics
Benzodiazepines
Beta blockers
Bladder antispasmodics
Dopamine agonists
General anesthetics
Opioid analgesics
Sedatives or hypnotics
Skeletal muscle relaxants
Sympathomimetics
Metabolic disturbances
Hepatic failure
Hypercalcemia
Hypermagnesemia
Hypoadrenalism/hyperadrenalism
Hypoglycemia/hyperglycemia
Hyponatremia/hypernatremia
Hypophosphatemia
Hypothyroidism/hyperthyroidism
Renal failure
Thiamine deficiency
Systemic diseases or conditions
Arrhythmia
Autoimmune conditions
Constipation
Dehydration
Heart failure
Hypercapnia
Hypertensive emergency
Hypothermia
Hypoxia
Myocardial infarction
Pain
Pancreatitis
Primary psychiatric conditions
Sleep deprivation
Urinary retention
Systemic infections
Acute viral (influenza, COVID-19, and others)
Intra-abdominal
Pneumonia
Sepsis
Urinary tract
Toxins
Alcohol (withdrawal or intoxication)
Illicit substances (withdrawal or intoxication)

Among the most common and important presentations of AMS is delirium, especially in older adults who are hospitalized.6,9 The hallmarks of delirium are acute, fluctuating changes in attention, awareness, and cognition that are not attributable to a neurocognitive disorder. Evidence of a secondary cause of AMS is often also present.6,9 Other features include sleep disturbances, hallucinations, delusions, inappropriate behavior, and emotional instability.11 Delirium was reviewed in a previous American Family Physician article.6

Evaluation

Changes in consciousness, appearance, behavior, mood, affect, or motor activity are usually apparent by general observation and interaction with the patient.

URGENT INTERVENTION

AMS can be caused by a life-threatening condition. Therefore, the first step in evaluating the patient is addressing abnormalities in the airway, breathing, and circulation (ABCs; Figure 1).2,3,10,1218

Once the ABCs have been stabilized, clinicians should evaluate for other conditions for which rapid intervention is needed to decrease the risk of morbidity and mortality. Abnormal vital signs may identify an obvious cause such as hypothermia, hypoxemia, or a hypertensive emergency, and such abnormalities should be addressed urgently.2,3,10

A point-of-care glucose level should be obtained, and if hypoglycemia is present, glucose should be administered immediately unless the patient is at risk of thiamine deficiency (e.g., alcoholism, gastric bypass surgery). Then thiamine must be administered before glucose to avoid Wernicke encephalopathy (i.e., AMS, oculomotor dysfunction, and ataxia due to thiamine deficiency).2,3,10

If concern exists for intracranial hemorrhage (e.g., anticoagulated state, head trauma) or ischemic stroke (e.g., focal abnormalities found during a neurologic examination), neuroimaging should be performed immediately to determine the next steps for care. Patients with a hemorrhage may require urgent surgery, and those with ischemic stroke can be triaged for reperfusion.2,3,10

Patients with status epilepticus need urgent anticonvulsive therapy and serum sodium testing. Patients with suspected sepsis require fluid resuscitation, urgent broad-spectrum antibiotics after cultures are obtained, and source control. Similarly, if meningitis is suspected, antibiotics at appropriate doses are urgently required following neuroimaging and lumbar puncture. If clinical suspicion is high and lumbar puncture will be delayed, antibiotics should be given empirically. When an opiate overdose is suspected, naloxone should be administered immediately.2,3,10

IDENTIFYING THE CAUSE OF AMS

After addressing the need for immediate interventions, a complete history should be obtained to identify the cause of a patient's AMS. A surrogate historian is often needed.2,3,9,10

Baseline cognitive function should be clarified. The timing of the onset of mental status changes is also important because abrupt and severe changes indicate a more serious pathology. The results of numerous observational assessments and answers to questions asked directly to the patient (when possible) can often suggest a cause13,10 (Table 31).

ComponentDefinition/contentWhat to assessSample questions/testsPotential diagnoses if abnormal
General observations
Appearance and behaviorBody habitus, eye contact, interpersonal style, style of dressAppearance: attention to detail, attire, distinguishing features (e.g., scars, tattoos), grooming, hygiene
Behavior: candid, congenial, cooperative, defensive, engaging, guarded, hostile, irritable, open, relaxed, resistant, shy, withdrawn
Eye contact: fleeting, good, none, sporadic
NADisheveled: depression, schizophrenia/psychotic disorder, substance use
Irritable: anxiety
Paranoid: psychotic disorder
Poor eye contact: depression, psychotic disorder
Provocative: personality disorder or trait
Mood and affectMood: subjective report of emotional state by patient
Affect: objective observation of patient's emotional state by physician
Body movements/making contact with others, facial expressions (tearfulness, smiles, frowns)How is your mood?
Have you felt sad/discouraged lately?
Have you felt energized/out of control lately?
Mood disorder, schizophrenia, substance use
Motor activityFacial expressions, movements, postureAkathisia: excessive motor activity (e.g., pacing, wringing of hands, inability to sit still)
Bradykinesia: psychomotor retardation (e.g., slowing of physical and emotional reactions)
Catatonia: immobility with muscular rigidity or inflexibility
NAAkathisia: anxiety, drug overdose or withdrawal, medication effect, mood disorder, posttraumatic stress disorder, schizophrenia
Bradykinesia: depression, medication effect, schizophrenia
Catatonia: schizophrenia/psychotic disorder, severe depression
Cognitive functioning
AttentionAbility to focus based on internal or external prioritiesCount by sevens or fives
Spell a word backward
Attention-deficit/hyperactivity disorder, delirium, mood disorder, psychotic disorder
Executive functioningOrdering and implementation of cognitive functions necessary to engage in appropriate behaviorsTesting each cognitive function involved in completing a taskOral Trail-Making Test: ask patient to alternate numbers with letters in ascending order (e.g., A1, B2, C3)Delirium, mood disorder, psychotic disorder, stroke
GnosiaAbility to name objects and their functionShow patient a common object (e.g., pen, watch, mobile phone) and ask if they can identify it and describe how it is usedStroke
LanguageVerbal or written communicationAppropriateness of conversation, rate of speech (> 100 words per minute is normal; < 50 words per minute is abnormal), reading and writing appropriate to education levelNARapid or pressured speech: mania
Slow or impoverished speech: delirium, depression, schizophrenia
Inappropriate conversation: personality disorder, schizophrenia
Limited literacy skills: depression
MemoryRecall of past eventsDeclarative: recall of recent and past events
Procedural: ability to complete learned tasks without conscious thought
When is your birthday?
What are your parents' names?
Where were you born?
Where were you on September 11, 2001?
Ask patient to repeat three words immediately and again in five minutes
Ask patient to sign their name while answering unrelated questions (each test must be tailored to the individual patient)
Short-term deficit: amotivation, attention-deficit/hyperactivity disorder, inattention, substance use
Long-term deficit: amnesia, dissociative disorder
OrientationAbility of patient to recognize their place in time and spaceTime, space, personWhat year/month/day/time is it?
What city/building/floor/room are you in?
What is your name? When were you born?
Amnesia, delirium, mania, severe depression
PraxisAbility to carry out intentional motor actsApraxia: inability to carry out motor acts; deficits may exist in motor or sensory systems, comprehension, or cooperationCould you show me how to use this hairbrush/hammer/pencil?Delirium, intoxication, stroke
ProsodyAbility to recognize the emotional aspects of languageRepeat “Why are you here?” with multiple inflections (e.g., happy, surprised, excited, angry, sad) and ask patient to identify the emotion
Ask the patient to say the same sentence with each of the above emotional inflections
Mood disorder, schizophrenia
Thought contentWhat the patient is thinkingDelusions, hallucinations, homicidality, obsessions, phobias, suicidalityDo you have thoughts or images in your head that you cannot get out?
Do you have any irrational or excessive fears?
Do you think people are trying to hurt you in some way?
Are people talking behind your back?
Do you think people are stealing from you?
Do you feel life is not worth living?
Do you see things that upset you?
Do you ever see/hear/smell/taste/feel things that are not really there?
Have you ever heard or seen something other people have not?
Have you ever thought about hurting others or getting even with someone who wronged you?
Have you ever thought about hurting yourself? If so, how would you do it?
Have you ever thought the world would be better off without you?
Delusions: fixed delusions, mania, psychotic disorder/psychotic depression
Hallucinations: delirium, mania, schizophrenia, severe depression, substance use
Homicidality: mood disorder, personality disorder, psychotic disorder
Obsessions: obsessive-compulsive disorder, posttraumatic stress disorder, psychotic disorder
Phobias: anxiety disorder, posttraumatic stress disorder
Suicidality: depression, posttraumatic stress disorder, substance use
Thought processesOrganization of thoughts in a goal-oriented patternCircumferential: patient goes through multiple related thoughts before arriving at the answer to a question
Disorganized thoughts: patient moves from one topic to another without organization or coherence
Tangential: patient listens to question and begins discussing related thoughts, but never arrives at the answer
Generally apparent throughout the encounterAnxiety, delirium, depression, schizophrenia, substance use
Visuospatial proficiencyAbility to perceive and manipulate objects and shapes in spaceAsk patient to copy intersecting pentagons or a three-dimensional cube on paper
Draw a triangle and ask patient to draw the same shape upside down
Delirium, stroke

Delirium is common but frequently overlooked, and is associated with serious medical conditions; therefore, assessment for delirium should always be considered in patients with acute AMS, especially in those at high risk(Table 4).6,9,11 The Confusion Assessment Method is a widely used, validated tool to identify delirium with a high sensitivity (94% to 100%) and specificity (90% to 95%)11 (Table 56). The 4 A's test is also a reliable screening tool (sensitivity of 89.7% and specificity of 84.1%) and is available at https://www.mdcalc.com/4-test-delirium-screening.11 The ultra-brief test requires only two questions—What is the day of the week? and Name the months of the year backwards—and has a sensitivity of 93% and specificity of 64%. The high sensitivity makes it useful to rule out delirium when both questions are answered correctly, but a positive test (i.e., incorrect answers) requires confirmation with a tool such as the Confusion Assessment Method.11,19

Age older than 65 years
Anesthesia
Baseline cognitive impairment
Baseline poor functional status
Change in environment
Constipation and/or urinary retention
Dehydration
Depression
History of alcohol misuse
History of delirium
Intensive care unit stay
Malnutrition
Medical illnesses (e.g., heart, lung, liver, kidney)
Polypharmacy
Sleep deprivation
Social isolation
Surgery
Tethers (e.g., urinary catheter, intravenous tubing)
Visual or hearing impairment
(1) Acute onset and fluctuating course
Is there evidence of an acute change in mental status from the patient's baseline? Did this behavior fluctuate during the past day (that is, did it tend to come and go or increase and decrease in severity)?
(2) Inattention
Does the patient have difficulty focusing attention; for example, being easily distracted or having difficulty keeping track of what was being said?
(3) Disorganized thinking
Is the patient's speech disorganized or incoherent; for example, rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?
(4) Altered level of consciousness
Overall, how would you rate this patient's level of consciousness: alert (normal); vigilant (hyperalert); lethargic (drowsy, easily aroused); stupor (difficult to arouse); coma (unarousable)?

A thorough medication history, including new or recent changes in prescription medications, over-the-counter medications, herbal products, and nutritional supplements, is essential. Consulting the patient's pharmacy may help with this task. Comorbid medical conditions, recent surgeries or procedures, and the use of alcohol and recreational drugs can increase the risk of or cause AMS and should be identified.2,3,9,10

Other aspects of the history should focus on associated symptoms or events of infection, trauma, neurologic changes, and headaches, any of which might identify a precipitating cause. A complete review of systems may uncover additional factors (e.g., constipation, urinary retention) contributing to AMS.2,3,9,10

PHYSICAL EXAMINATION

The neurologic examination is important to identify AMS and determine the cause. In addition to the mental status examination, cranial nerves, motor function, reflexes, sensation, and coordination should be evaluated. Focal abnormalities can suggest intracranial pathology such as stroke, neoplasm, or demyelinating conditions. If a patient is exhibiting asterixis, it suggests metabolic encephalopathy.13,10,12

Attention to eye and vision abnormalities can also provide important diagnostic clues. Visual field defects can indicate a stroke. Pupillary abnormalities may be present with substance abuse, stroke, or pending cerebral herniation. The ability to perform extraocular movements may differentiate a suspected comatose patient from one with a locked-in syndrome. Ophthalmoplegia is an important finding of Wernicke encephalopathy, and nystagmus can identify drug intoxication or stroke. Papilledema suggests increased intracranial pressure.2,3,10

Examination of the head, ears, nose, and throat should focus on signs of trauma and infection. When examining the neck, thyroid abnormalities and meningismus are important findings that suggest thyroid disorders and nervous system infections, respectively. Examination of the heart, lungs, and abdomen can indicate important systemic causes of AMS, such as heart failure, pneumonia, and decompensated hepatic disease.2,3,10

Examination of the skin can show signs of chronic systemic disease (e.g., jaundice), systemic infection (e.g., petechiae), or local infection with cellulitis or abscess, or locate medication patches. A musculoskeletal examination may identify inflamed joints indicating infection or an autoimmune condition.2,3,10

A genitourinary and rectal examination can identify infection. The rectal examination can show gastrointestinal bleeding or neurologic compromise when tone is reduced.2,3,10

TESTING

The history and physical examination guide diagnostic testing; however, the following initial tests can be considered for all patients with AMS when the diagnosis is not clear: complete blood count, electrolytes, liver function tests, serum ammonia, blood urea nitrogen, creatinine, phosphorus, magnesium, blood gas analysis, thyroid testing, blood culture, urinalysis, viral antigen or polymerase chain reaction tests when community prevalence is high, toxicology screening, chest radiography, and electrocardiography. 2,3,10

Considering that the above tests are noninvasive and relatively inexpensive, they should be used liberally, especially when the etiology is not clear from the history and physical examination. Additional tests to consider when initial evaluation is not diagnostic are adrenal function, erythrocyte sedimentation rate, C-reactive protein, extended toxicology screening, and serologic testing for autoimmune disorders.2,3,10

NEUROIMAGING

Unless the etiology is clear and the risk of intracranial pathology is low, neuroimaging should be included in the initial assessment of recent AMS.1214 Patients with trauma, anticoagulation, hypertension, hypertensive emergency, headache, nausea or vomiting, clinical concern for infection, new-onset seizure, neurologic findings on examination, history of cancer, older age, and a known intracranial process all require imaging. Neuroimaging should be performed in patients who did not previously receive imaging and in whom initial therapy has failed. In patients with new-onset delirium, imaging should be considered if there is no other obvious precipitating cause.13

Noncontrast computed tomography (CT) of the head is the initial study for most patients. Noncontrast CT is widely available, can be completed quickly, identifies most pathology requiring urgent intervention, and is better tolerated by patients than magnetic resonance imaging (MRI). If MRI is available and tolerated by the patient, it can also be the initial imaging study and is preferred to CT if the progression of an inflammatory process (e.g., multiple sclerosis) is suspected. Contrast is helpful when infection, tumor, inflammatory pathology, or vascular abnormalities are suspected.1315

MRI should be considered when CT was the initial study but was not diagnostic; it can detect pathology not evident on CT such as acute, minor, or posterior circulation ischemia, encephalitis, subtle subarachnoid hemorrhages, and inflammatory conditions. MRI may also be indicated to better define pathology found on CT.1315

LUMBAR PUNCTURE

Lumbar puncture can help identify several causes of AMS, including meningitis, encephalitis, subarachnoid hemorrhage, autoimmune conditions, and metastases to the subarachnoid space. When there is clinical suspicion for meningitis, a lumbar puncture is mandatory. Standard testing of cerebrospinal fluid includes a cell count with differential, protein, glucose, and culture. Obtaining additional fluid for freezing is prudent because other testing may be needed.2,3,20

For patients with immunosuppression, the threshold for lumbar puncture should be low, and testing for infectious agents will need to be broadened beyond standard testing. Consulting an infectious disease specialist should be considered for these patients.2,3

Patients with AMS have an increased risk of intracranial pathology that could result in cerebral herniation from a lumbar puncture. Therefore, neuroimaging should be done before performing a lumbar puncture.2,3,21

ELECTROENCEPHALOGRAPHY

Electroencephalography is an important study to rule out nonconvulsive seizures, which may occur in 8% to 30% of patients with AMS without an obvious cause.16 It can also help diagnose metabolic encephalopathy and infectious encephalitis.17,18 A normal electroencephalogram may help exclude a suspected seizure disorder and support a primary psychiatric cause of AMS.

PATIENTS WITH UNDERLYING DEMENTIA

Patients with dementia have an increased risk of AMS.6,9,11 Clinicians are often challenged to determine if deficits are chronic or new, and substantial efforts should be made to identify the patient's baseline status. Clinicians should balance the risk of unnecessary testing and intervention for chronic situations the clinician may be unaware of vs. missing a new treatable condition causing AMS. Advance directives and input from the family can help guide evaluation and treatment decisions.

A common pitfall for patients with dementia who are in a care facility is inappropriately attributing AMS to a urinary tract infection. Many patients who are institutionalized have asymptomatic bacteriuria, and treatment is not indicated unless a urinary infection with symptoms is present.22 Management should focus on identifying other causes for the patient's AMS.

Prevention

When patients are at risk of AMS, particularly for delirium, nonpharmacologic preventive measures can decrease incidence, especially in those who are hospitalized.6,9,11 The use of multiple measures through a multidisciplinary team approach is most effective. There is no convincing evidence to support the use of medications to prevent AMS or delirium.6,9,11

Treatment

Definitive therapy for AMS is treatment of the underlying causes or the removal of precipitating agents. However, when patients' behaviors threaten themselves or others before a reversible cause can be identified or fully treated, intervention is needed to avoid harm. In these situations, nonpharmacologic interventions are the treatment of choice.2,3,6,10,11

NONPHARMACOLOGIC TREATMENTS

Reassurance and use of de-escalation techniques by staff, family, or friends can be effective. Reducing artificial lighting and other environmental stimuli such as monitoring alarms can also help calm patients. A family member or assigned staff can stay at the patient's bedside to ensure that patients do not harm themselves. Additional measures include those used for AMS or delirium prevention (Table 66,9,11).

Adequate hydration
Adequate nutrition
Adequate oxygenation
Avoid constipation
Avoid tethering (intravenous lines, monitors, Foley catheter)
Cognitively stimulating activities
Early mobilization
Ensure patient has assistive devices (eyeglasses, hearing aids, mobility devices)
Geriatric specialty consultation
Infection prevention
Limit psychoactive medications
Pain management
Presence of family and caretakers
Orientation (accurate calendars and clocks, and appropriate lighting; reorientation by staff and family)
Sleep enhancement measures (avoid nighttime disturbances, use appropriate lighting, reduce noise at night)

Physical restraints are not considered standard interventions and should rarely be used, and then only as a last resort and for the shortest time possible.2,6,911

MEDICATION

Medication to manage behaviors associated with AMS should be used only when nonpharmacologic measures are not effective, and then only when it is essential to control behavior. Studies evaluating the effectiveness of medications used for their sedative effects yield conflicting results and may cause harm due to adverse effects.11,23,24 Antipsychotics have historically been used off-label to treat delirium; however, a recent systematic review does not support the use of these agents in hospitalized adults with delirium.24 Anti-psychotics also carry a U.S. Food and Drug Administration boxed warning about an increased risk of death when used in older adults with dementia-related psychosis.

Benzodiazepines should generally be avoided unless they are being used to treat alcohol withdrawal or seizures because they may worsen delirium. For any agent, the lowest effective dose for the minimum time necessary should be used. Medications used when nonpharmacologic modalities fail are listed in eTable A.

DrugDose* and routeMaximum daily dosageOnsetTreatment considerations
AntipsychoticsFDA boxed warning: increased mortality in older patients with dementia-related psychosis
Adverse effects: extrapyramidal symptoms, QTc prolongation, increased risk of falls, aspiration
Droperidol2.5 to 10 mg IV20 mg3 to 10 minutes
5 to 10 mg IM20 mg3 to 10 minutes
Haloperidol0.5 to 1 mg orally every four to six hours30 mg15 to 30 minutes
0.5 to 1 mg IM/IV every 30 to 60 minutes30 mg5 to 20 minutes
Olanzapine (Zyprexa)5 to 10 mg IM30 mg15 minutes
2.5 to 5 mg orally20 mg30 to 60 minutes
Quetiapine (Seroquel)12.5 to 25 mg orally150 mg15 to 45 minutes
Ziprasidone (Geodon)5 to 10 mg IM40 mg15 minutes
BenzodiazepinesMay worsen delirium
Generally reserved for alcohol withdrawal and seizures
Lorazepam (Ativan)0.5 to 2 mg IM/IV/orally10 mg3 to 5 minutes
Midazolam2 to 5 mg IM/IV20 mg1 to 10 minutes
Ketamine0.5 to 1 mg per kg IV200 mg0.5 minutesUse caution in patients with cardiovascular disease; may increase blood pressure and heart rate
4 to 5 mg per kg IM500 mg3 to 4 minutes

Data Sources: PubMed (including use of the Clinical Queries feature), the Cochrane Database of Systematic Reviews, Essential Evidence Plus, and UpToDate were searched using the key terms altered mental status and encephalopathy. Also searched were specific etiologies of altered mental status. Search dates: January 19 to February 22, 2021, and August 20, 2021.

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