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

This clinical content conforms to AAFP criteria for CME.

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

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