Diagnosis AMS: A Comprehensive Guide for Emergency Department Assessment

Author Credentials

Author 2019: Al’ai Alvarez MD, Stanford University, Palo Alto, CA

Author 2008: Tom Morrissey, MD, University of Florida, Jacksonville, Florida

Editor: Navdeep Sekhon, Baylor College of Medicine, Houston, TX.

Last Updated: September, 2019

Case Study: The 3 AM “AMS” Patient

The call comes in at 3 am on a Saturday. The emergency department nurse informs you about a new patient transfer from a local nursing home. The chief complaint: “AMS” – altered mental status. The patient is an 87-year-old female, bed-bound, and minimally verbal. A quick review of the EMS report and nursing home documentation reveals a complex medical history including diabetes, multi-infarct dementia, schizoaffective disorder, seizure disorder, and chronic abdominal pain. This scenario is a stark reminder of the diagnostic challenges frequently encountered in the ED when faced with patients presenting with AMS.

Introduction: Unraveling the Enigma of Altered Mental Status

Diagnosing altered mental status (AMS) in the emergency department (ED) is often a formidable task. While some cases present clear-cut etiologies, such as a postictal state following a seizure or hypoglycemia in a known diabetic patient, many others are far more ambiguous. These subtle presentations demand meticulous attention to detail, reliance on historical data from diverse sources, and a high degree of clinical suspicion to uncover potentially life-threatening underlying conditions.

Altered mental status, often referred to as AMS, is not a disease entity itself but rather a symptom, a manifestation of an underlying disturbance. The spectrum of potential causes is vast, ranging from easily reversible conditions like hypoglycemia to irreversible damage from intracranial hemorrhage, and from relatively benign states such as alcohol intoxication to critical emergencies like meningitis or encephalitis. This expansive differential diagnosis necessitates a structured and systematic approach to effectively evaluate, diagnose, and manage patients presenting with AMS. Developing proficiency in the Diagnosis Ams is crucial for emergency medicine professionals to ensure optimal patient care and outcomes.

Objectives: Mastering the Diagnosis and Management of AMS

Upon completion of this module, you will be able to:

Recognize the Pivotal Role of History: Appreciate the critical significance of historical factors obtained from various sources in accurately diagnosing the underlying causes of AMS.
Classify AMS Presentations: Identify and differentiate the three primary classifications of AMS: delirium, dementia, and psychosis, understanding their distinct characteristics.
Construct a Differential Diagnosis: Develop a comprehensive differential diagnosis for AMS based on a synthesis of patient history and thorough physical examination findings.
Systematic Diagnostic Approach: Construct a logical and efficient approach to the diagnostic workup and subsequent management of patients presenting with AMS in the emergency setting.
Formulate Initial Management Strategies: Develop effective initial management plans tailored to address a wide range of potential causes of AMS, focusing on rapid stabilization and targeted interventions.
Plan Appropriate Patient Disposition: Strategically plan the disposition of patients with AMS, considering factors such as etiology, severity, and available resources to determine the most suitable level of care.

Initial Actions and Primary Survey: The ABCDEF Approach to Rapid Assessment

In the fast-paced environment of the emergency department, all patients necessitate an immediate primary survey to identify and address any immediate life threats. The “ABCDEF approach” provides a structured framework for this initial assessment, simultaneously offering an opportunity to identify and correct rapidly reversible causes of AMS. This crucial first step should ideally commence as the patient is being connected to monitoring equipment and intravenous access is being established.

Airway: Begin by ensuring a patent and protected airway. Assess for any obstructions such as secretions or vomitus requiring suctioning. Open the airway using appropriate maneuvers, continuously monitor pulse oximetry, and administer supplemental oxygen as needed. Hypoxia represents a readily reversible cause of AMS that must be promptly addressed.
Breathing: Evaluate the patient’s respiratory effort and adequacy. Inadequate ventilation can lead to elevated carbon dioxide levels (hypercapnia) and respiratory acidosis, both of which can contribute to AMS. If ventilation is compromised, initiate positive pressure ventilation until adequate spontaneous respiration is restored. In patients with depressed respiratory status and AMS, consider the possibility of narcotic overdose as a reversible cause.
Circulation: Assess the circulatory status thoroughly. Palpate for strong distal pulses, evaluate blood pressure for extremes of hypertension or hypotension, and determine the cardiac rhythm. Observe for signs of hypoperfusion such as diaphoresis, and assess skin temperature for warmth or coolness and clamminess. Hypoperfusion deprives the brain of essential oxygen and glucose, leading to AMS. Non-perfusing cardiac rhythms necessitate immediate initiation of CPR and Advanced Cardiac Life Support (ACLS) protocols. Hypotension should prompt rapid intravenous fluid boluses and a concurrent, urgent investigation into the underlying cause. Consider the judicious use of point-of-care ultrasonography (POCUS) to aid in rapid assessment of circulatory status.
Disability: Conduct a rapid neurological disability assessment. Employ the Glasgow Coma Scale (GCS) or the Alert Verbal Painful Unresponsive (AVPU) scale (detailed below) for a swift evaluation of the patient’s level of consciousness. Observe for any seizure-like activity or signs suggestive of a postictal state, such as loss of bowel or bladder control, lingual trauma, or the presence of nystagmus or fasciculations. Assess pupil size, equality, and reactivity to light. Pay close attention to spontaneous movements, noting any asymmetry. Unilateral lack of movement may indicate stroke, while bilateral lack of movement below a certain level could suggest an acute spinal cord syndrome. If there is any suspicion of trauma, cervical spine immobilization should be immediately implemented.
Exposure: Completely undress the patient to facilitate a comprehensive head-to-toe examination. Carefully inspect for any signs of trauma, the presence of transdermal drug patches, dialysis access sites, potential sources of infection (such as indwelling catheters), or petechiae. Accurately measure the patient’s core temperature and promptly address any extremes of hypothermia or hyperthermia.
Fingerstick Blood Sugar: Perform a point-of-care fingerstick blood glucose measurement in every patient presenting with AMS. Hypoglycemia is a common, potentially fatal, yet readily reversible cause of altered mental status that must be excluded in all cases.

Alt text: Point-of-care glucose testing using a glucometer, essential for diagnosing hypoglycemia as a cause of altered mental status.

Throughout these initial stabilization steps, remain vigilant for rapidly reversible etiologies of AMS. Hypoglycemia and narcotic overdose are prevalent causes that can be swiftly managed with dextrose and naloxone, respectively. At a minimum, every patient with AMS warrants:

Assessment and stabilization of the ABCs
Continuous cardiac monitoring and pulse oximetry
Supplemental oxygen administration if hypoxic or exhibiting respiratory distress
Point-of-care glucose testing
Establishment of intravenous access
Thorough evaluation for signs of trauma, with consideration for cervical spine stabilization
Empiric naloxone administration if narcotic overdose is suspected
Consideration of point-of-care ultrasound (POCUS) if the patient is in shock or undifferentiated hypotension.

Differential Diagnosis: Navigating the Expansive Landscape of AMS Etiologies

The differential diagnosis for altered mental status is remarkably extensive. In addition to historical information and physical examination findings, patient-specific factors such as age, pre-existing medical conditions, geographic location, and even the time of year (e.g., winter – raising suspicion for carbon monoxide toxicity in colder climates) can significantly broaden the differential considerations in a patient presenting with AMS.

Similar to many common complaints or presenting symptoms in emergency medicine, it is practically impossible to create an exhaustive list encompassing all potential causes of AMS. However, when evaluating a patient with AMS, it is beneficial to organize the differential diagnosis along several distinct pathways. Table 1 provides a framework for categorizing causes of AMS based on underlying pathophysiology, including structural lesions or primary central nervous system (CNS) dysfunction, toxic-metabolic insults, and infectious etiologies.

Table 1. Differential Diagnosis for AMS by System
Primary CNS/Structural
Metabolic/Autoregulatory
Pharmacologic/Toxic
Infectious
Other

Alternatively, the mnemonic AEIOU-TIPS (Table 2) is a widely used and effective tool for generating a broad differential diagnosis for AMS, providing a structured approach to recall common and critical etiologies.

Table 2. AEIOU TIPS: A Mnemonic for Causes of AMS
A
E
I
O
U
T
I
P
S

Classic Presentation: Deconstructing the Vague Symptom of AMS

Unfortunately, there is no singular “classic presentation” that definitively characterizes a patient with AMS. The terms “altered mental status” and “altered level of consciousness” (ALOC) are frequently used in clinical practice, but they remain inherently vague and non-specific descriptors. Similarly, terms like lethargy and obtundation describe degrees of decreased consciousness but are more subjective assessments than objective findings. The broad “AMS” label can be applied to patients ranging from those who are postictal to individuals with pre-existing dementia, highlighting the wide spectrum of presentations.

The varied presentations of AMS can range from global CNS depression to confusion, and paradoxically, to agitation. Therefore, clear and precise terminology is essential when documenting and communicating a patient’s mental status.

Three broad classifications of AMS are commonly recognized and clinically relevant: delirium, dementia, and psychosis (Table 3). Differentiating between these categories is crucial as they have distinct underlying causes, treatment strategies, and disposition considerations. In most cases, a detailed history and thorough physical examination are sufficient to initially categorize a patient into one of these three entities, guiding subsequent diagnostic and therapeutic approaches for diagnosis ams.

Dementia: Chronic Cognitive Decline

Dementia is typically a chronic, slowly progressive neurodegenerative process that is primarily managed in the outpatient setting by primary care physicians and neurologists. Emergency department encounters involving patients with dementia often arise when caregivers are no longer able to manage the patient’s care at home. In these situations, the “emergency” is frequently related to safety concerns, social support deficits, and the need for placement rather than an acute medical deterioration of the dementia itself. Admission may be necessary to ensure patient safety, conduct a thorough social assessment, and arrange for appropriate placement if home care is no longer feasible.

When assessing a patient with known dementia in the ED, it is crucial to establish the patient’s cognitive baseline. Obtaining collateral history from family members or caregivers is paramount to determine if there has been a new, acute change in mental status superimposed on the chronic dementia. Such an acute change should raise strong suspicion for delirium, a more immediate and potentially reversible medical emergency.

Delirium: An Acute Medical Emergency

Delirium represents a genuine medical emergency requiring prompt recognition and intervention. As defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V), the key diagnostic features characterizing delirium are:

Disturbance in Attention and Awareness: Reduced ability to direct, focus, sustain, and shift attention, coupled with a diminished awareness of the environment.
Acute Onset and Fluctuating Course: The disturbance develops acutely over a short period (typically hours to days), represents a discernible change from the patient’s baseline cognitive function, and tends to fluctuate in severity throughout the day.
Additional Cognitive Disturbance: Presence of an additional cognitive deficit, which may manifest as memory impairment, disorientation, language difficulties, visuospatial dysfunction, or perceptual disturbances.
Not Better Explained by Pre-existing Neurocognitive Disorder: The cognitive disturbances are not more appropriately explained by a pre-existing, evolving, or established neurocognitive disorder (such as dementia) and do not occur exclusively in the context of a severely reduced level of arousal, such as coma.
Evidence of Underlying Medical Etiology: There is evidence from the history, physical examination, or laboratory investigations to suggest that the disturbance is a direct physiological consequence of an underlying medical condition, substance intoxication or withdrawal, or medication side effect.

Additional clinical features that may accompany delirium and contribute to diagnostic clarity include:

Psychomotor Behavioral Disturbances: These can range from hypoactivity (reduced motor activity and slowed responses) to hyperactivity (restlessness, agitation, increased sympathetic nervous system activity), as well as disruption of normal sleep-wake cycles.
Variable Emotional Disturbances: Patients with delirium may exhibit a wide range of emotional states, including fear, anxiety, depression, euphoria, irritability, or perplexity.

Isolated structural lesions within the brain are exceedingly unlikely to affect both the brainstem and bilateral cortical structures extensively enough to induce delirium while still allowing the patient to survive. Delirium is almost invariably caused by an underlying systemic medical problem that exerts toxic or metabolic effects on the brain. Systematic screening for delirium in all patients presenting with AMS is critical, as many cases are caused by reversible conditions. Promptly recognizing delirium is potentially life-saving. Delirium carries a poor prognosis if the underlying cause remains unidentified and unaddressed.

Psychosis: Hallucinations and Delusions

Psychosis is characterized by the presence of hallucinations (sensory perceptions in the absence of external stimuli) and/or delusions (fixed, false beliefs) without insight into their unreality. These psychotic symptoms can be profoundly disturbing to the patient and frequently provoke agitation and distress. While pharmacologic interventions have a role in managing acute psychosis, creating a calm and peaceful environment can significantly alleviate patient agitation. Simple non-pharmacologic interventions, such as speaking to the patient with respect in a non-threatening manner and placing them in a quiet, less stimulating room, can be remarkably helpful in de-escalating acute psychotic episodes.

A key differentiating feature of psychosis, particularly in distinguishing it from delirium and dementia, is that orientation to person, place, and time is often preserved in patients experiencing psychosis. This relative preservation of orientation can be a valuable clinical clue in the diagnosis ams and differentiating psychosis from other causes of altered mental status.

Neurologic Causes: Focal Deficits Mimicking AMS

Certain focal neurologic deficits can be mistakenly interpreted as alterations in consciousness if not carefully assessed. Dysarthria (difficulty articulating speech) and aphasia (language impairment, encompassing receptive, motor, or mixed types), spatial neglect syndromes (unawareness of one side of space), and even hemianopsia (visual field loss in half of the visual field) and hemiparesis (unilateral weakness) can be misconstrued as confusion or AMS if a thorough neurological examination is not performed. A detailed neurological assessment is essential to distinguish focal neurologic deficits from true alterations in mental status and ensure accurate diagnosis ams.

Detailed History and Physical Exam: Cornerstones of AMS Evaluation

History: Gathering Crucial Information from Multiple Sources

Patients presenting with AMS, by definition, are often unable to provide a comprehensive and reliable medical history themselves. Therefore, obtaining historical information from ancillary sources becomes absolutely indispensable. Family members, friends, caregivers, nursing home staff, and any witnesses to the patient’s presentation are invaluable sources of information. Making a concerted effort to contact and interview these individuals is essential to accurately ascertain the nature of the change in mental status, its temporal pattern, and potential contributing factors. The following are examples of key questions that can be directed to these informants to help differentiate the underlying issue(s) contributing to AMS and guide diagnosis ams:

“Can you describe what is different about [patient’s name] today compared to their usual self?” Probing further with: “What is [patient’s name] like on a typical good day? Are they able to cook or do laundry independently? Can they navigate around the house on their own? Can they be left alone safely? Are they able to engage in a conversation about current events?”

“Can you elaborate on how they are different today?” Seeking specific descriptions: “Are they more withdrawn or unusually quiet? Or are they more agitated or restless than usual? Do they seem confused or excessively forgetful? Have they been hallucinating or saying things that don’t make sense?”

“When did this change in mental status begin?” Exploring the temporal pattern: “Did this change come on suddenly and abruptly, or has it developed gradually over time? Is the altered mental status constant, or does it fluctuate throughout the day (waxing and waning)? Has this type of episode happened before? If so, was a diagnosis made at that time? Have there been any recent changes to their medications, either starting new medications or stopping existing ones? (Medication side effects or interactions are common culprits.)”

“What do you think might have caused this change?” Exploring potential triggers or contributing factors: “Does [patient’s name] manage their own medications? Are they prone to falls? Is it possible they could have accidentally ingested someone else’s medications or household poisons? Is there a family history of similar conditions in parents or siblings? Have there been any significant stressful life events recently, such as a hospitalization, loss of a loved one, or moving to a new or unfamiliar environment?”

Actively screen for delirium: Numerous validated screening tools are available to aid in the detection of delirium. One of the simplest and most widely used is the Confusion Assessment Method (CAM), particularly the CAM for the Intensive Care Unit (CAM-ICU) for non-verbal patients. The CAM algorithm assesses for: 1) acute onset and fluctuating course of mental status changes, 2) inattention, and either 3) disorganized thinking or 4) altered level of consciousness. If the patient meets criteria for features 1, 2, and either 3 or 4, the likelihood of delirium is very high.

Inquire about pre-existing medical conditions that may predispose to AMS or manifest as AMS during decompensation. Specifically, ask about a history of:

Diabetes mellitus (risk of diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic nonketotic state (HHNK))
Hypertension (potential for hypertensive encephalopathy or medication-induced hypotension)
Endocrine disorders (thyroid disease, Addison’s disease)
Renal insufficiency or failure
Cancer (paraneoplastic syndromes, electrolyte imbalances such as hypernatremia or hypercalcemia)
Pre-existing dementia
Cardiovascular and cerebrovascular disease (stroke risk)
Seizure disorders (including nonconvulsive status epilepticus)
Psychiatric disorders

Medication effects are a particularly common and often overlooked cause of AMS, especially in elderly patients. A meticulous review of all medications, including prescription medications, over-the-counter drugs, herbal supplements, and home remedies, is absolutely critical. Specifically, inquire if the patient has recently started any new medications or discontinued any previously prescribed medications.

Physical Exam: Unveiling Clues Through Systematic Assessment

A comprehensive head-to-toe physical examination is frequently invaluable in uncovering clues to the underlying cause of AMS. Ensure the patient is fully undressed to allow for a complete examination, leaving no area unexamined. (It is often surprising where critical findings, such as a fentanyl patch, may be discovered.) The Glasgow Coma Scale (GCS) (Table 4) is a standardized and widely used tool to quantify and communicate a patient’s level of consciousness to other healthcare providers.

While the GCS was originally designed to predict outcomes after head trauma, and its use in guiding intubation decisions (“GCS less than 8, intubate!”) is common, it has not been formally validated for this specific purpose. Furthermore, inter-rater reliability studies have shown a 1-2 point variability in GCS scores between individual evaluators. Despite these limitations, the GCS remains a rapid, practical, and useful tool for broadly communicating a patient’s overall level of arousal.

The physical examination can yield vital information to guide the diagnosis ams. The following is a systematic approach to key components of the physical exam, focusing on features relevant to AMS:

Vital Signs:

Fever: Is the patient febrile? Fever may indicate an infectious etiology, such as meningitis, encephalitis, or systemic sepsis.
Heart Rate: Is the patient bradycardic or tachycardic? Bradycardia may suggest medication overdose (e.g., beta-blockers, calcium channel blockers), increased intracranial pressure, or hypothermia. Tachycardia may be a response to pain, anxiety, dehydration, sepsis, or withdrawal syndromes.
Respiratory Rate: Is the patient bradypneic or tachypneic? Bradypnea may be seen in opioid overdose, increased intracranial pressure, or central nervous system depression. Tachypnea may be compensatory for metabolic acidosis, hypoxia, or pulmonary pathology.
Blood Pressure: Is the patient hypotensive or severely hypertensive? Hypotension can result from hypovolemia, sepsis, cardiogenic shock, or medication effects. Hypertension can be a cause (hypertensive encephalopathy) or a consequence (pain, anxiety) of AMS.

Neurologic Status:

Level of Alertness: Assess the patient’s general level of alertness.
GCS Score: Calculate and document the Glasgow Coma Scale score.
AVPU Scale: Utilize the AVPU scale (Alert, Verbal, Pain, Unresponsive) as a quick screening tool. Always supplement with a verbal description of the patient’s responsiveness and interaction.
Maintain Wakefulness: How difficult is it to keep the patient aroused and engaged? Does the patient drift back to sleep easily?

Content of Thought and Speech:

Attention and Focus: Can the patient maintain focus and attention during conversation?
Speech Content: Is their speech tangential, circumstantial, or incoherent?
Orientation: Is the patient appropriately oriented to person, place, and time?
Perseveration: Does the patient repeatedly ask the same questions or get stuck on certain phrases (perseveration)?
Internal Stimuli: Is the patient reacting to internal stimuli, such as hallucinations or delusions?

Assess for Focal Motor Findings:

Weakness or Pronator Drift: Is there any unilateral weakness or pronator drift suggestive of a focal neurological deficit?
Cranial Nerve Exam: Perform a cranial nerve examination, paying particular attention to pupillary size, equality, and reactivity, as well as extraocular movements.
Nystagmus: Observe for nystagmus, which may suggest intoxication, medication effects, or cerebellar pathology.
Brainstem Lesion Suspicion: Remember that the brainstem is the region where isolated structural or ischemic lesions can directly cause decreased arousal. Decreased level of consciousness accompanied by cranial nerve abnormalities should be considered a brainstem lesion until proven otherwise.

Evaluate for Tremulousness or Abnormal Reflexes:

Asterixis, Palmomental Reflex, Glabellar Tap: Assess for asterixis (flapping tremor of the hands), palmomental reflex (stroking the palm elicits chin muscle contraction), and glabellar tap reflex (persistent blinking to repetitive taps on the forehead). These reflexes can be abnormal in metabolic encephalopathies and withdrawal states.
Focal Motor Findings: Re-emphasize assessment for focal motor deficits, as these can also be present in withdrawal states or metabolic derangements.

Cardiovascular Exam:

Arrhythmias: Are there any cardiac arrhythmias, such as atrial fibrillation, that may predispose to embolic stroke?
Murmurs: Auscultate for heart murmurs, which may suggest endocarditis (a potential source of sepsis and embolic phenomena).
Peripheral Circulation: Evaluate for evidence of adequate peripheral circulation.
Pulmonary Findings: Auscultate the lungs for findings suggestive of pneumonia (a common cause of sepsis) or pulmonary edema (potential cause of hypoxia).
Carotid Bruits: Auscultate for carotid bruits, which may indicate carotid artery stenosis and increased stroke risk.

Abdominal Exam:

Signs of Portal Hypertension: Look for signs of portal hypertension, such as ascites, caput medusae, and spider angiomata, which may suggest hepatic encephalopathy.
Abdominal Tenderness: Palpate the abdomen for tenderness, guarding, or rebound tenderness, which could indicate appendicitis, intussusception, or another intra-abdominal source of sepsis, including cholangitis or mesenteric ischemia. Be mindful that elderly patients may not always present with classic signs of infection, such as leukocytosis or fever.

Genitourinary and Rectal Exam:

Urinary Output: Assess urinary output. Decreased output may suggest uremic encephalopathy. Consider point-of-care ultrasound (POCUS) to evaluate the bladder and kidneys.
Signs of Infection: Look for signs of urinary tract infection, vaginal infection, prostatic infection, or perineal infection.
Melena or Rectal Bleeding: Assess for melena or blood in the stool, which could indicate an upper gastrointestinal bleed. Uremia and hyperammonemia can occur secondary to upper GI bleeding and contribute to AMS.

Skin, Extremity, Musculoskeletal Exam:

Petechiae: Examine the skin for petechiae, which may suggest meningococcemia or thrombocytopenia.
Dialysis Graft: Note the presence of a dialysis graft, which may suggest uremic encephalopathy or increased risk of intracranial hemorrhage due to platelet dysfunction.
Track Marks: Look for track marks from intravenous drug use, which may indicate substance abuse or infection risk.
Transdermal Drug Patches: Carefully inspect for transdermal drug patches (e.g., fentanyl, scopolamine), which may be contributing to AMS.
Jaundice: Assess for jaundice, which may suggest hepatic encephalopathy.
Nuchal Rigidity or Meningismus: Evaluate for nuchal rigidity or other signs of meningismus, which are suggestive of central nervous system infection or subarachnoid hemorrhage.
Signs of Trauma: Look for signs of trauma, such as raccoon’s eyes, Battle’s sign, or hemotympanum, which may indicate head trauma.

Alt text: Clinical photograph demonstrating Battle’s sign, postauricular ecchymosis indicative of basilar skull fracture in a patient with altered mental status.

Infectious Sources: Identify any obvious sources of infection, such as decubitus ulcers, cellulitis, or abscesses.
Masses or Lymphadenopathy: Palpate for masses or lymphadenopathy, which might suggest underlying malignancy and paraneoplastic syndromes.

In many cases, a detailed history and physical examination are sufficient to categorize the patient’s change in mental status as delirium, dementia, or psychosis, guiding the direction of further diagnostic testing and management strategies for diagnosis ams.

Diagnostic Testing: Targeted Investigations to Confirm Etiology

Generally, diagnostic testing should be guided by the differential diagnosis generated from the history and physical examination and should be used to rule in or rule out specific conditions. Indiscriminate “shotgun” testing is generally discouraged. However, in the setting of undifferentiated AMS, a more liberal approach to diagnostic studies is frequently warranted due to the broad differential diagnosis and the potentially high-stakes consequences of delaying appropriate treatment.

It is helpful to consider the major categories of potential causes for AMS and utilize the following diagnostic tests if these categories cannot be confidently excluded based on history and physical examination alone.

Metabolic or Endocrine Causes:

Rapid Glucose: Point-of-care glucose testing is mandatory for all AMS patients.
Serum Electrolytes: Serum sodium (Na+), potassium (K+), chloride (Cl-), bicarbonate (HCO3-), calcium (Ca+). Electrolyte imbalances are common causes of AMS.
Basic Metabolic Panel (BMP): The serum bicarbonate level within the BMP can help assess the degree of metabolic acidosis and may provide clues to a broad differential diagnosis of metabolic acidosis (consider the mnemonic CAT-MUDPILES).
Blood Urea Nitrogen (BUN) and Creatinine: Elevated BUN/creatinine may indicate uremia as a cause of AMS, or potentially an upper gastrointestinal bleed if the BUN is disproportionately elevated compared to creatinine.
Arterial Blood Gas (ABG) or Venous Blood Gas (VBG) with Co-oximetry: ABG or VBG with co-oximetry is helpful to assess for hypoxemia, hypercarbia, and to evaluate for carboxyhemoglobinemia (carbon monoxide poisoning) or methemoglobinemia if clinically suspected.
Thyroid Function Tests: Thyroid Stimulating Hormone (TSH) and Free T4 to evaluate for hypothyroidism or hyperthyroidism.
Serum Ammonia Level: Consider measuring serum ammonia level if hepatic encephalopathy or certain metabolic disorders are suspected.
Serum Cortisol Level: In specific cases, serum cortisol level may be indicated to evaluate for adrenal insufficiency (Addisonian crisis).

Toxic or Medication Causes:

Medication Levels: Measure serum levels of relevant medications, such as anticonvulsants (valproic acid, phenytoin, carbamazepine), digoxin, theophylline, lithium, etc., if medication toxicity is suspected.
Electrocardiogram (EKG): Obtain an EKG to assess for medication-induced cardiac effects. Certain medications like tricyclic antidepressants (TCAs) can prolong the QTc interval, while lithium can cause various arrhythmias.
Drug Screen: Urine and/or serum drug screen to detect the presence of benzodiazepines, opioids, barbiturates, stimulants, etc.
Ethanol Level: Measure serum ethanol level to assess for alcohol intoxication.
Serum Osmolality: Calculate or measure serum osmolality if toxic alcohol ingestion (methanol, ethylene glycol) is suspected.

Infectious Causes:

Blood Cultures: Obtain blood cultures to evaluate for bacteremia or sepsis.
Complete Blood Count (CBC) with Differential: CBC with differential to assess white blood cell count (leukocytosis or leukopenia), platelet count, and differential cell counts, which can be suggestive of infection.
Serum Lactic Acid: Measure serum lactic acid if the patient meets systemic inflammatory response syndrome (SIRS) criteria or if sepsis or septic shock is suspected. Elevated lactate can be a marker of severe sepsis or hypoperfusion.
Urinalysis and Urine Culture: Urinalysis and urine culture to evaluate for urinary tract infection.
Chest X-ray: Chest X-ray to evaluate for pneumonia.
Lumbar Puncture (LP) with Opening Pressure: Consider lumbar puncture to evaluate cerebrospinal fluid (CSF) for meningitis or encephalitis. Crucially, always obtain a CT scan of the head prior to lumbar puncture if there is any suspicion of increased intracranial pressure (ICP) or a focal neurological deficit to rule out mass effect and prevent potential herniation.

Traumatic Causes:

Head CT and Cervical Spine CT: Head CT (typically without contrast initially) and cervical spine CT are indicated if trauma is suspected based on history or physical examination.
Point-of-Care Ultrasound (POCUS): POCUS can be used in trauma assessment (eFAST exam) to rapidly evaluate for hemoperitoneum or pneumothorax.
Chest and Pelvis X-ray: Chest and pelvis X-rays may be indicated in trauma evaluation.
Other Imaging Modalities: Consider other imaging modalities (CT angiography, MRI) as clinically indicated based on the suspected mechanism and extent of trauma.

Neurologic Causes:

Head CT: Head CT (usually non-contrast initially for suspected stroke or trauma) is often the initial neuroimaging modality.
Brain MRI: Brain MRI may be indicated if brainstem or posterior fossa pathology is suspected, or for more detailed evaluation of suspected stroke, encephalitis, or demyelinating disease.
Carotid/Vertebral Artery Ultrasound: Carotid and vertebral artery ultrasound (Doppler) can be used to evaluate for carotid artery stenosis or vertebral artery abnormalities in suspected cerebrovascular disease.
Electroencephalogram (EEG): EEG is indicated if non-convulsive status epilepticus is suspected.

Hemodynamic Instability Causes:

Point-of-Care Ultrasound (POCUS) including Bedside Echocardiography: POCUS, including bedside echocardiography, can be used to assess cardiac function, volume status, and identify pericardial effusion in patients with hemodynamic instability.
Electrocardiogram (ECG): ECG to evaluate for cardiac ischemia, arrhythmias, or conduction abnormalities.
Cardiac Enzymes: Consider measuring cardiac enzymes (troponin) if myocardial infarction (silent MI in elderly) is suspected as a contributing factor.

How to Make the Diagnosis: Integrating Clinical and Diagnostic Data

Exercise caution when applying Occam’s razor in the diagnosis ams. While seeking a single unifying diagnosis is natural and often correct, mental status changes are frequently multifactorial. A definitive diagnosis is often not assured until identified abnormalities have been addressed, appropriate treatment initiated, and the patient’s mental status has returned as close as possible to their baseline. Sometimes, the diagnosis and resolution are rapid and clear-cut (e.g., dextrose reversing hypoglycemia, naloxone reversing opioid overdose). However, more often, significant improvement may take hours or even days to manifest.

Initial diagnostic maneuvers are primarily guided by the history and physical examination findings. These clinical clues allow for the formulation of a working differential diagnosis categorized by the major etiologic categories. Presumptive treatment is often initiated concurrently (see below). Diagnostic imaging and laboratory tests are ordered to narrow down the differential diagnosis and confirm the underlying etiology for diagnosis ams. Remember, in emergency medicine, diagnosis and treatment are iterative and dynamic processes. As treatment is initiated, frequent reassessment of the patient is crucial. How is the patient responding to interventions? The patient’s clinical response often either confirms the initial diagnostic suspicion or prompts a re-evaluation and consideration of alternative diagnoses.

In some cases, a definitive diagnosis may not be established within the ED setting. For instance, the diagnosis of dementia requires comprehensive neuropsychological testing beyond the scope of emergency practice. Similarly, primary psychiatric disorders cannot be definitively diagnosed and managed in a single ED visit. Physicians specializing in these areas rely on emergency physicians to exclude underlying organic causes of behavioral changes. Therefore, a “negative workup” for organic etiologies in the ED can be just as diagnostically valuable as a “positive” finding. Exercise extreme caution in clearing a patient for psychiatric evaluation without a thorough investigation for organic causes of AMS. While there are no specific laboratory tests mandated to “clear” a patient for psychiatric evaluation, a meticulous history and physical examination are imperative. Any abnormal vital signs, physical findings, or diagnostic test results should be considered red flags, warranting further investigation. When in doubt, it is always prudent to err on the side of caution and pursue further medical evaluation.

Treatment: Addressing the Underlying Pathology

Beyond immediate interventions to address life-threatening conditions such as impending cardiopulmonary collapse, treatment for AMS should be primarily directed at correcting or treating the underlying pathology causing the altered mental status. Table 5 outlines treatment strategies for selected potential causes of AMS.

| Table 5. Treatment for Selected Causes of Altered Mental Status |
|—|—|
| Disease Process | General Treatment |
|—|—|
| Hypoglycemia | Dextrose administration (IV D50 or oral glucose). Note that one ampule of D50 (50% dextrose) only contains 100 calories. May need to provide ongoing glucose source (oral intake or continuous IV dextrose infusion) to prevent rebound hypoglycemia. |
| Opioid overdose | Naloxone administration (IV, IM, or intranasal). Be aware that naloxone has a relatively short half-life compared to some opioids, particularly long-acting opioids like methadone. Consider longer observation periods and potential redosing or continuous naloxone infusion. |
| Agitated withdrawal states (alcohol, benzodiazepine) | Supportive care, including fluid resuscitation, electrolyte repletion, and sedation with benzodiazepines (e.g., lorazepam, diazepam). Be aware of the potential for excited delirium in severe withdrawal, a true medical emergency with high mortality requiring careful and cautious management. |
| Dehydration/Hypovolemia | Intravenous fluid resuscitation with isotonic crystalloids (normal saline or lactated Ringer’s solution). |
| Infection (sepsis, meningitis, encephalitis) | Antibiotics, antiviral medications (for viral encephalitis), or antifungal agents as appropriate, tailored to the suspected pathogen and site of infection. |
| Hypothermia/Hyperthermia | Active warming measures for hypothermia (e.g., warm blankets, forced air warming, warm IV fluids) or cooling measures for hyperthermia (e.g., evaporative cooling, cooling blankets, ice packs, and in severe cases, ice water immersion). |
| Medication Overdose/Toxic Ingestions | Supportive care, including airway management, hemodynamic support, and specific antidotes if available. Common antidotes include: fomepizole or ethanol (for methanol or ethylene glycol poisoning), pyridoxine (vitamin B6) for isoniazid toxicity, digoxin-specific antibody fragments (Digibind/Digifab) for digoxin toxicity. |
| Hypertensive Encephalopathy | Controlled reduction of blood pressure using intravenous antihypertensive agents such as nitroprusside, labetalol, nicardipine, or other appropriate agents. Avoid precipitous drops in blood pressure. |
| Hyponatremia | Hypertonic saline (3% NaCl) is indicated for symptomatic hyponatremia with seizures or altered mental status. The rate and extent of sodium correction should be guided by the acuity and severity of symptoms. Rapid correction of chronic hyponatremia carries a risk of central pontine myelinolysis. |
| CNS lesion causing vasogenic edema (tumor, abscess) | Glucocorticoids (dexamethasone) to reduce vasogenic edema and intracranial pressure. |
| Wernicke’s Encephalopathy (thiamine deficiency) | Thiamine administration (intravenous thiamine is preferred initially). |

Disposition: Tailoring Care to Individual Patient Needs

The majority of patients presenting to the emergency department with altered mental status will require hospital admission for further evaluation, definitive diagnosis ams, and ongoing management. However, in carefully selected cases, patients with acute alterations in mental status that are rapidly reversed in the ED and who demonstrate stable clinical status may be safely discharged home. Classic examples of this subset of patients include:

Seizure: Patients with known seizure disorders who present with breakthrough seizures due to subtherapeutic anticonvulsant levels may be considered for discharge if their anticonvulsant medications can be appropriately reloaded in the ED, and reliable follow-up with their neurologist or primary care physician can be assured. However, it is crucial to be vigilant for secondary causes of breakthrough seizures, such as trauma, infection, myocardial infarction, or sleep deprivation, which may necessitate admission.
Hypoglycemia: Diabetic patients who are found to be transiently hypoglycemic and who rapidly improve clinically after dextrose administration may be discharged if a clear and reversible cause of hypoglycemia is identified (e.g., missed meal, excessive insulin dose), they are not taking long-acting hypoglycemic agents, and appropriate supervision and safe follow-up are in place. Remember that D50 provides only a limited caloric load, and sustained euglycemia requires ongoing glucose intake. Ensure adequate observation time in the ED to confirm a positive trajectory of serum glucose levels.
Narcotic overdose: Patients who have experienced opioid overdose and have been successfully treated with naloxone in the ED, demonstrating sustained reversal of respiratory depression and AMS, may be considered for safe discharge, particularly if the overdose was clearly accidental and not intentional. However, be cautious with longer-acting narcotics like methadone, as the effects of naloxone may wear off before the opioid is fully metabolized, leading to resedation. Furthermore, it is essential to consider the possibility of non-accidental overdose and assess for suicidal ideation or self-harm risk before discharge.

Factors Influencing Disposition Decisions:

The disposition of a patient presenting with AMS is highly variable and depends on a complex interplay of factors:

Patient Acuity: How acutely ill is the patient? Are there ongoing life threats or hemodynamic instability?
Etiology of AMS: Is the underlying cause of AMS identifiable and readily reversible?
Treatment Efficacy: Has the underlying cause been effectively addressed in the ED?
Return to Baseline: Has the patient’s mental status returned to their premorbid baseline?
Risk of Recurrence: Is there a high likelihood of recurrence of AMS?
Social Support: If recurrence is possible, is there adequate social support at home to recognize recurrent AMS and ensure timely return to medical care?

The decision to admit a patient to an intensive care unit (ICU) versus a general hospital ward is guided by factors such as hemodynamic instability, the underlying etiology of AMS, the anticipated clinical course, the need for close monitoring, airway management concerns, and available institutional resources.

Patients Refusing Care: Navigating Capacity and Autonomy

Patients with mild alterations in mental status may become frustrated with the ED evaluation process and express a desire to leave the hospital against medical advice (AMA). This situation presents a significant challenge for emergency physicians. Often, the underlying cause of AMS is not immediately apparent, and the potential risks associated with AMS are substantial. However, respecting patient autonomy and the right to refuse medical care is also paramount. The critical question becomes: Does the patient possess medical decision-making capacity?

Our responsibility as healthcare providers in such situations revolves around the determination of capacity. Specifically, does the patient have the mental capacity to understand the ramifications of refusing recommended medical care and leaving the hospital AMA? To demonstrate capacity, the patient must be able to understand both the risks of leaving AMA and the benefits of staying for continued evaluation and treatment. Involve family members and friends in the discussion, as they may be able to persuade the patient to remain for necessary care. Negotiation can sometimes be helpful: “I understand your frustration with the wait. Would you be willing to wait for just one more test that could help us understand what’s going on?” Observing the patient over time can provide further insight into their lucidity and decision-making abilities. Address basic needs: Has the patient eaten recently? Are there other psychosocial needs that can be addressed in the ED to improve their comfort and cooperation?

When uncertainty persists regarding capacity or patient safety, it is always prudent to err on the side of caution. The legal framework in most jurisdictions provides some protection to healthcare providers who hospitalize patients against their will when it is deemed medically necessary and justified to prevent harm. Make a diligent effort to explain the situation clearly to family members and enlist their support in encouraging the patient to stay. Thoroughly document the clinical reasoning, assessment of capacity, and actions taken in the patient’s medical record.

Pearls and Pitfalls in Diagnosis AMS

Pitfall: Failure to recognize subtle changes in behavior as clinically significant. Pearl: Actively seek historical information from witnesses and LISTEN attentively to their accounts!
Pitfall: Failure to recognize AMS, particularly delirium, as a symptom of serious underlying medical illness. Pearl: Always consider AMS as a potential indicator of a significant medical condition requiring thorough investigation.
Pitfall: Failure to actively search for and treat easily remediable causes of AMS (hypoglycemia, opioid overdose, etc.). Pearl: Prioritize rapid assessment for and treatment of reversible etiologies in all patients with AMS.
Pitfall: Allowing a patient with AMS (including intoxicated patients) to sign out against medical advice (AMA) without assessing medical decision-making capacity, discussing with family, and thoroughly documenting the encounter. Pearl: Always carefully assess capacity, involve family, and meticulously document all aspects of AMA discharges in patients with AMS.

Case Resolution:

Returning to the initial case presentation: A quick review of the patient’s medication list revealed a recently initiated prescription for valproic acid for her seizure disorder. You promptly addressed the ABCs, ruled out hypoglycemia and opioid overdose (considering her chronic abdominal pain and long-term narcotic use). As laboratory results returned, you noted a markedly elevated valproic acid level of 176 ug/ml (toxic range). Recognizing the association between valproic acid toxicity and hyperammonemia-induced AMS, you initiated carnitine therapy (which can aid in valproic acid detoxification) and admitted the patient to the ICU. Over the subsequent three days, with supportive care and management of valproic acid toxicity, the patient’s mental status improved significantly, and she was ultimately discharged back to the nursing home with a revised antiepileptic medication regimen, highlighting the importance of considering medication toxicity in the diagnosis ams.

References/Further Reading

American College of Emergency Physicians: Clinical policy for the initial approach to patients presenting with altered mental status. Ann Emerg Med. 1999;33:251-280.

Ely EW, Inouye SK, Bernard DG, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001;286:2703-2010.

Han JH, Zimmerman EE, Cutler N, et al. Delirium in older emergency department patients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med. 2009;16:193-200.

Koita J, Riggio S and Jagoda A. The mental status examination in emergency practice. Emerg Med Clin N Am. 2010;28:439-451.

Kanich W, Brady VJ, Huff JS, et al. Altered mental status: evaluation and etiology in the ED. Am J Emerg Med. 2002;20:613-617.

Simon JR MD PhD. Refusal of care: the physician-patient relationship and decision making capacity. Ann Emerg Med. 2007;50(4):456-461.

Starkman S and Wright S. Altered Mental Status. In: Emergency Medicine. An Approach to Clinical Problem Solving. Hamilton GC, Sanders AB, Strange GR and Trott AT Eds. WB Saunders and Co. 2003. 517-534.

The American Psychiatric Association’s Diagnostic and Statistical Manual, 5th edition (DSM-V), Neurocognitive Disorders Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. May 2013