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
It’s 3 am on Saturday. The nurse lets you know about the new patient that was just sent over from the local nursing home with a chief complaint of “AMS”. She’s 87 years old, bed-bound and minimally verbal. A quick review of the EMS sheet and nursing home paperwork show a history of diabetes, multi-infarct dementia, schizoaffective disorder, seizure disorder and chronic abdominal pain.
Diagnosing a patient with a change in mental status can be a daunting challenge in the Emergency Department (ED). Some presentations are clear; a patient who is postictal after a seizure or a diabetic patient who is hypoglycemic. At times the clinical picture is more subtle and not easily identified. Enlisting historical data from multiple sources and maintaining a high index of suspicion is necessary to detect the behavioral marker of potentially catastrophic pathology.
Altered mental status (AMS) is not a disease: it is a symptom. Causes run the gamut from easily reversible (hypoglycemia) to permanent (intracranial hemorrhage) and from the relatively benign (alcohol intoxication) to life threatening (meningitis or encephalitis). The differential diagnoses are enormous. Developing a structured and systematic approach to these cases will help you develop and streamline the diagnostic workup and management of these patients with AMS.
Upon completion of this self-study module, you should be able to:
- Recognize the importance of historical factors in diagnosing causes of AMS
- Identify the three most common classifications of AMS
- List a differential diagnosis for AMS based on history and physical findings
- Construct an approach to the diagnostic workup and management of a patient with AMS
- Formulate an initial management of many causes of AMS
- Plan the disposition of a patient with AMS
Initial Actions and Primary Survey
All emergency department patients require an initial assessment for immediate threats. The “ABCDEF approach” provides a good opportunity to check for quickly reversible causes of AMS. Ideally this should happen as the patient is being placed on a monitor and IV access is being established.
- Airway: Check to see that the airway is open and is being protected. Are there secretions or vomit that needs to be suctioned? Open the airway, check pulse-oximetry and provide supplemental oxygen if needed. Hypoxia is a potentially reversible cause of AMS.
- Breathing: Assess breathing. Inadequate ventilation will lead to elevated levels of CO2 (respiratory acidosis) and can cause AMS. Positive pressure ventilation should be provided until adequate ventilation can be restored. In a patient with AMS with a depressed respiratory status, consider narcotic overdose as a possible cause.
- Circulation: Assess circulatory status. Can you feel good distal pulses? Is the blood pressure very high or low? What is the cardiac rhythm? Is the patient diaphoretic? Does the patient feel warm to touch? Cool and clammy? Hypoperfusion starves the brain of oxygen and glucose and leads to AMS. Nonperfusing rhythms require immediate CPR and ACLS. Hypotension should prompt IV fluid bolus and an immediate search for the cause. Consider point-of-care ultrasonography (POCUS).
- Disability: Check for neurologic disability. Use Glasgow Coma Score (GCS) or Alert Verbal Painful Unresponsive (AVPU) scale (see below) for a quick assessment of level of consciousness. Look for seizure-like activity or signs of post-ictal state—loss of bowel or bladder tone, lingual trauma, or active nystagmus or fasciculations. Are the pupils equal and reactive? Pay attention to spontaneous movements. Lack of movement on one side of the body night indicate stroke while lack of movement below a certain level of the body could indicate an acute spinal cord syndrome. If there is any suspicion of trauma the cervical spine should be stabilized.
- Exposure: Fully undress and perform a rapid head to toe look for signs of trauma, transdermal drug patches, dialysis access, infectious sources (such as catheters) or petechiae. Pay attention to the patient’s core temperature, and address extremes.
- Fingerstick Blood Sugar: Hypoglycemia is common, deadly and reversible cause of altered mental status that should be assessed in all altered patients.
As you proceed through the above steps of initial stabilization, keep in mind rapidly reversible causes for the AMS. Hypoglycemia and narcotic overdose are very common causes of AMS and can easily be managed with dextrose and naloxone respectively. At a minimum, all AMS patients deserve:
- Assessment of the ABC’s
- Cardiac monitoring and pulse oximetry
- Supplemental oxygen if hypoxic or if in respiratory distress
- Point-of-care glucose testing
- Intravenous access
- Evaluation for signs of trauma with consideration for c-spine stabilization
- Consider naloxone administration if narcotic overdose is suspected
- Consider point of care ultrasound (POCUS) if the patient is in shock
The differential diagnosis of AMS is exhaustive. In addition to history and physical exam findings, factors such as the patient’s age, medical co-morbidities, geographic location and time of year (e.g. winter – carbon monoxide toxicity in cold weather climate zones) further expand the differential diagnosis for the patient with AMS.
Like many complaints or presentations, it is impossible to list all possible causes. In the case of a patient with an AMS, your differential diagnosis can develop along a number of different pathways. Table 1 may assist you as you develop your differential diagnosis. This table organizes causes of AMS occurring as a result of a structural lesion or primary CNS dysfunction, toxic, metabolic or infectious insults.
Alternatively, a mnemonic that is commonly used to help generate a differential diagnosis for AMS is AEIOU-TIPS (see Table 2).
Unfortunately, there is no classic presentation for a patient with AMS. The terms, “Altered mental status” and “altered level of consciousness” (ALOC) are common acronyms, but are vague nondescript terms. The same can be said about terms such as lethargy or obtundation. Both represent some level of decreased consciousness but are more subjective descriptors than true objective findings. The “AMS” label may be applied to a patient who is postictal or perhaps a patient who has dementia. Because the varied presentations that can range from global CNS depression to confusion to the other extreme, agitation, it is important to be clear with terminology on how we describe a patient’s mental status.
Three common broad classifications of AMS include delirium, dementia and psychosis (see Table 3). It is important to keep these in mind as you assess your patient because they have very different causes, treatments and dispositions. The table below describes fundamental differences between these three entities. History and physical exam are almost always enough to classify your patient into one of the categories.
Typically, dementia is a slow, progressively degenerative process that is managed by primary care physicians and neurologists rather than in the ED. Sometimes families bring a patient with dementia to the ED and the true “emergency” is that they are no longer able to care for the patient at home. Admission may be necessary for safety, social assessment and placement.
It is important when assessing the patient with dementia to establish the patient’s baseline; getting collateral information is imperative to ensure that there is no new, acute change in the patient’s mental status which can be a sign of delirium which is a more immediate concern.
Delirium represents a true medical emergency. As defined by the DSM-V the five key features characterizing delrium are:
- Disturbance in attention (reduced ability to direct, focus, sustain, and shift attention) and awareness.
- The disturbance develops over a short period of time (usually hours to days), represents a change from baseline, and tends to fluctuate during the course of the day.
- An additional disturbance in cognition (memory deficit, disorientation, language, visuospatial ability, or perception).
- The disturbances are not better explained by another preexisting, evolving or established neurocognitive disorder, and do not occur in the context of a severely reduced level of arousal, such as coma.
- There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by a medical condition, substance intoxication or withdrawal, or medication side effects.
- Additional features that may accompany delirium and confusion include the following:
- Psychomotor behavioral disturbances such as hypoactivity, hyperactivity with increased sympathetic activity, and impairment in sleep duration and architecture.
- Variable emotional disturbances, including fear, depression, euphoria, or perplexity.
Isolated structural lesions are incredibly unlikely to involve brainstem and bilateral cortical structures and still leave the patient alive. Delirium is almost always caused by an underlying medical problem that has toxic or metabolic effects on the brain. Screening for delirium in all altered patients is critical since many have reversible causes. Recognizing delirium can be lifesaving. Delirium has a very poor prognosis unless the underlying cause is recognized and addressed.
Psychosis can be defined as the presence of hallucinations and/or delusions without insight. Quite often the hallucinations/delusions can be quite disturbing to the patient and provoke agitation. While there is a role for medications in the acutely psychotic, creating a calm, peaceful environment for the patient can comfort their agitation. Simple interventions like speaking to the patient with respect in a non-threatening way and placing in a quiet room can be quite helpful.
An important differentiating aspect of psychosis is that their orientation is often intact, which can help differentiate from delirium and dementia.
Some focal neurological deficits can be mistaken for alterations in consciousness. Dysarthria and aphasia (receptive, motor or mixed), spatial neglect syndromes, even hemianopsia and hemiparesis can be mistaken as confusion if not looked at closely.
Detailed History and Physical Exam
Patients with AMS are, by definition, difficult to elicit a comprehensive and detailed history. Family, friends, caretakers, nursing home staff, and/or witnesses are all invaluable sources of information. Make the effort to contact them to ascertain the nature of the change in mental status. Below are some questions that can be asked of others to help differentiate the underlying issue(s) relating to AMS.
Can you tell me what you see different about your grandmother? → What’s she like on a good day? Does she cook/do laundry for herself? Can she get around the house on her own? Can she be left alone? Can she hold a conversation about current events?
Can you describe how she is different? → Is she more quiet/agitated? Is she confused or forgetful? Is she hallucinating?
When did this change start? → Did this change come on suddenly or over some time? Is it continuous or does it wax and wane (identify pattern)? Has it ever happened before (previous diagnosis)? Have there been any changes in her medicines recently (medication side effects)?
What do you think might have caused this? → Does she administer her own medicines? Is she prone to falls? Could she have gotten into someone else’s medicines or household poisons? Does she have parents or siblings with similar conditions? Have there been any significant stressful events lately such as hospitalization, loss of a loved one or moving to an unfamiliar environment?
Screen for delirium: → Many screening tools are available. One of the simplest is the confusion assessment method:CAM-ICU. If the patient has an acute or fluctuating course, evidence of inattention and either disorganized thinking or an altered level of consciousness (elevated or decreased), they have a very high likelihood of having delirium.
Many medical conditions manifest as AMS during decompensation. Look for a history of:
- Diabetes (DKA, HHNK),
- Hypertension (hypertensive encephalopathy or medication overdose)
- Endocrine disease (thyroid, Addison’s disease)
- Renal failure
- Cancer (paraneoplastic syndromes, Na+, Ca++)
- Cardiovascular and cerebrovascular disease
- Seizure (including nonconvulsive status epilepticus)
- Psychiatric disorders
Medication effects are also very common causes of AMS in the elderly. A detailed review of medications (including nonprescription, health supplements, home remedies) is critical. Has the patient recently started or stopped any medications?
A detailed head to toe physical exam will often yield clues as to the cause. Fully undress and examine the entire patient. Do not leave a square inch unexamined (you would be amazed where you will find a fentanyl patch sometimes). The Glasgow Coma Scale (Table 4) can be quite helpful to help communicate to other providers a patient’s mental status:
GCS score was designed to predict outcome after head trauma. Although we frequently use it to help decide who needs aggressive management (“less than eight, intubate!”), it has never been validated for that purpose. Further, there is often a 1-2 point disagreement between individual evaluators. It is, however, a quick and useful way to communicate overall level of arousal.
The physical exam can be quite helpful in trying to discover what is causing a patient’s altered mental status. Below is a list of important features/questions to answer as physician goes through their physical exam.
Does the patient have a fever?
Is the patient bradycardic or tacycardic?
Is the patient bradypneic or tachypneic?
Is the patient hypotensive or severely hypertensive?
Level of alertness
GCS score (see above)
AVPU scale (A=alert, V=responds to verbal stimuli, P=responds to painful stimuli, U=unresponsive). A verbal description is helpful
How difficult is it to keep the patient awake?
Content of thought and speech
Can the patient stay focused?
Is their speech content tangential?
Is the patient appropriately oriented?
Does the patient keep asking the same questions over and over (perseveration)?
Are they reacting to internal stimuli?
Assess for focal motor findings
- Is there weakness or pronator drift?
- Cranial nerve exam (especially pupils)
- Do you see nystagmus?
- Remember, the brainstem is where isolated structural or ischemic lesions can cause decreased arousal. Decreased level of consciousness with cranial nerve findings is a brainstem lesion until proven otherwise.
Evaluate for tremulousness or abnormal reflexes
Focal motor findings as above are common in withdrawal states or metabolic derangement/encephalopathy.
Are there arrhythmias (a-fib) that predispose to embolic strokes?
Is there a murmur? endocarditis?
Is there evidence of good peripheral circulation?
Are there pulmonary findings that indicate pneumonia (sepsis) or pulmonary edema (hypoxia)?
Are there bruits over the carotid arteries?
Is there ascites, caput medusa, spider angiomata or other signs of portal hypertension? (hepatic encephalopathy)?
Is the abdomen tender (appendicitis, intussusception, abdominal sepsis source including cholangitis, mesenteric ischemia)? Remember that elderly patients may not always mount leukocytosis or fever.
Genitourinary and rectal exam
Is the patient making urine (uremic encephalopathy)? Consider POCUS to evaluate the bladder and kidneys
Are there signs or urinary, vaginal, prostatic or perineal infection?
Is there melena or blood in the stool? Uremia and hyperammonemia may occur secondary to upper GI bleed.
Skin, extremity, musculoskeletal exam
Are there petechiae (meningococcemia, thrombocytopenia)?
Is there a dialysis graft (uremic encephalopathy, intracranial hemorrhage due to dysfunctional platelets)?
Are there track marks from injection drug abuse?
Are there transdermal drug patches?
Is the skin jaundiced (hepatic encephalopathy)?
Is there nuchal rigidity or meningismus (CNS infection, subarachnoid hemorrhage)?
Are there signs of trauma (raccoon’s eyes, Battle’s sign, hemotympanum)?
Are there infectious sources noted (decubitus ulcers, cellulitis, abscesses)?
Are there masses or lymphadenopathy that might indicate cancer (paraneoplastic syndromes)?
History and physical exam findings are usually enough to help you categorize the change in mental status as delirium, dementia or psychosis. Further testing should be ordered as below to help narrow or confirm the differential diagnosis within each of these categories of AMS.
Generally, diagnostic testing is used to rule in or rule out items on your differential diagnosis and should not be ordered in a “shot-gun” fashion. In the case of a patient with an undifferentiated AMS presentation, however, liberal use of diagnostic studies is frequently necessary because of the breadth of the differential diagnosis and the high stakes involved in delaying appropriate treatment.
It is helpful to think of the main categories of causes for AMS and use the below diagnostic testing if any of these categories cannot be ruled out by H&P alone.
Metabolic or Endocrine causes
- Rapid glucose
- Serum electrolytes (Na+, Ca+)
- Serum bicarbonate in the basic metabolic panel helps assess degree of acidosis and may clue to a broad differential diagnosis (CAT-MUDPILES).
- BUN/Creatinine (uremia, upper GI bleed)
- ABG or VBG (with co-oximetry for carboxy- or met-hemoglobinemia)
- Thyroid function tests
- Serum Ammonia level
- Serum cortisol level
- Toxic or medication causes
Levels of medications (anticonvulsants, digoxin, theophylline, lithium, etc.)
- EKG (certain medications such as TCA can prolong QTc and others like lithium cause other arrhythmias)
- Drug screen (benzodiazepines, opioids, barbiturates, etc.)
- Ethanol level
- Serum osmolality (toxic alcohols)
- Blood cultures
- CBC with differential
- Serum lactic acid if meets systemic immune response syndrome (marker for severe sepsis or septic shock)
- Urinalysis and culture
- Chest X-ray
- Lumbar puncture (with opening pressure); always obtain a CT scan of the head prior to lumbar puncture if you suspect an increased intracranial pressure (ICP).
- Head CT/ cervical spine CT
- Chest and Pelvis X-ray
- Other imaging modalities as indicated
- Head CT (usually start without contrast for trauma or CVA)
- MRI (if brainstem/posterior fossa pathology suspected)
- Carotid/vertebral artery ultrasound
- EEG (if non-convulsive status epilepticus suspected)
- Hemodynamic instability causes
- POCUS including bedside echocardiography
- Cardiac enzymes (silent MI)
How do I make the diagnosis?
Be careful using Occam’s razor in diagnosing the cause of AMS. We would all like to find a single unifying cause for what ails our patients, and frequently the simplest, most straightforward answer is the correct one. Mental status changes, however, are often multifactorial. Diagnosis is never assured until abnormalities have been recognized, addressed, and the patient has returned as close to their baseline mental status. Sometimes this is quick and clear (dextrose reversing hypoglycemia or naloxone reversing a heroin overdose), but often it takes hours or days to see significant improvement.
Initial diagnostic maneuvers are primarily determined by the history and physical exam findings. These clues will allow you to build a working differential diagnosis based on the major categories that cause. Often presumptive treatment is begun at this point (see below). Diagnostic imaging and laboratory tests are ordered to narrow down or confirm the differential diagnosis. Remember, in Emergency Medicine, diagnosis and treatment is a dynamic process. As treatment is initiated, it is important to frequently reassess the patient. How are they responding to the interventions? Their response is often what cinches the diagnosis or reminds us to look in a different direction.
In some cases, the diagnosis will not be definitively made in the ED. Dementia requires neuropsychiatric testing beyond our scope of practice. Psychiatric disorders cannot be adequately diagnosed and treated in a single ED visit. The physicians who can make these diagnoses do rely on Emergency Physicians to rule out other organic causes of behavioral changes. Thus, our negative work-up can be just as important as our positive ones. Be very careful about clearing a patient for psychiatric evaluation without close investigation for organic causes. While there are no specific laboratory tests required to clear a psychiatric patient, a thorough history and physical is imperative. Any abnormal vital signs, physical findings or diagnostic tests should be viewed as red flags. When in doubt, err on the side of caution.
Beyond interventions required for the immediate life threats such as impending cardiopulmonary collapse, treatment should be geared towards correcting/treating the underlying pathology. A list of treatments (Table 5) for potential causes of AMS is listed in the table below.
The majority of patients with an AMS will require hospitalization. Sometimes, however, patients with acute alterations of their mental status that are easily reversed and observed to be stable in the emergency department can safely be discharged home. Classic examples of this subset of patients includes:
- Seizure: Patients with known seizure disorders found to have low anticonvulsant levels may be discharged if medications can be loaded and appropriate safe follow-up can be assured. Be vigilant for other causes of break-through seizures including trauma, infection, MI, or lack of sleep.
- Hypoglycemia: Diabetic patients found to be transiently hypoglycemic and improve with dextrose may be discharged if a clear reason can be found, they are not on long acting agents, and appropriate supervision and safe follow-up can be assured. Again, D50 is only 100 calories and requires that you observe the patient at least over an appropriate time to get a positive trajectory of their serum glucose levels.
- Narcotic overdose: When properly treated and observed in the emergency department, these patients may be safely discharged home. Beware of longer acting narcotics such as methadone. It is also important to consider non-accidental overdoses. Is the patient having thoughts of self-harm?
Disposition of the patient presenting with AMS is highly variable and dependent on many factors:
- How sick is the patient?
- Is the cause identifiable and easily reversed?
- Has the cause been addressed?
- Did the patient return to baseline?
- Is the situation likely to return?
- If it does return, is there adequate social support to recognize it and bring the patient in for medical care?
The decision to admit the patient to an ICU setting as opposed to the hospital ward may be based on hemodynamic stability, etiology of the AMS, expected course, need for close monitoring, airway management issues and institutional resources.
What if a patient does not recognize their need for treatment and wants to leave the hospital?
Patients with mild alterations in mental status frequently get frustrated and want to leave the hospital. This poses a special problem for emergency physicians. Often, we are not able to quickly ascertain the underlying cause for the change in behavior. We recognize the potential dangers in this presenting complaint, but also want to respect patient autonomy and respect decisions. Does the patient have medical decision-making capacity?
Our responsibility as healthcare providers often revolves around the determination of capacity: specifically, does the patient have the mental capacity to understand the ramifications of refusing care and leaving the hospital against medical advice. The patient will need to demonstrate that they understand both the risk of leaving against advice and the benefit of staying. Solicit the help of family and friends. They may be able to convince the patient to stay for treatment. Often, negotiating with time helps: “I understand you’re frustrated and have been waiting a long time. Are you willing to wait for this one test to help us help you?” The test of time allows us to further evaluate the patient’s lucidity, and the result may help sway the patient’s decision to stay longer. Has the patient eaten? What other psychosocial needs does this patient have that you may be able to address?
When in doubt, err on the side of caution. Our profession gives us some protection regarding hospitalizing patients against their will, when we think it is medically necessary and justified. Make the effort to explain the situation to family members and enlist their help. Clearly document the reasons behind your thought processes and actions on the chart.
Pearls and Pitfalls
- Failure to recognize subtle changes in behavior as significant. Seek historical witnesses and LISTEN to them!
- Failure to recognize AMS, especially delirium as a symptom of serious medical illness.
- Failure to look for and treat easily remediable causes.
- Allowing an AMS (including intoxicated) patient to sign out “against medical advice” without talking to family and clearly documenting that the patient has medical decision-making capacity.
A quick review of the patient’s medication included a new prescription for valproic acid for her seizure disorder. You immediately addressed the ABC’s and ruled out hypoglycemia and opiate overdose (recall that she has chronic abdominal pain and is on long standing narcotics). As the laboratory studies return, you noted her valproic acid level to be elevated to 176 ug/ml (high). As the astute provider, you recalled that valproic acid toxicity elevates the ammonia level which can lead to AMS. You initiated carnitine therapy and admitted the patient to the ICU. Three days later, the patient is sent back to the nursing home with a new antiepileptic drug.
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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