Altered Mental Status in the Emergency Department

Austin T. Smith, MD; Jin H. Han, MD, MSc


Semin Neurol. 2019;39(1):5-19. 

In This Article


When the immediately life-threatening conditions have been excluded or managed, a detailed and accurate history should be obtained. A significant challenge to this goal is that patients with AMS are frequently unable to provide an accurate history, even in those with subtle alterations.[112] For this reason, it is critically important that an accurate history be obtained from a collateral historian who knows the patient well and can describe the events that proceeded the changes in mental status. Usually this collateral historian is a family member, caregiver, or friend. If the patient is from a skilled nursing facility, the patient's nurse should be contacted by phone.


Most patients presenting to the ED present with acute changes (minutes to days) rather than gradual (months to years). In general, acute changes are more likely to be life-threatening, particularly if the changes are abrupt (seconds) and/or are associated with profound changes in mental status (RASS ≤ −2 or ≥ +2).[7] An abrupt (seconds) change in mental status may also suggest a cerebrovascular event, especially in the presence of focal neurologic findings.

Associated Symptoms

Any preceding illnesses, concurrent symptoms, or other associated symptoms should be determined. Any recent focal neurologic symptoms, even if brief and resolved, should raise suspicion for stroke, as transient ischemic attacks are a major risk factor for the development of a stroke.[113,114] Fevers, chills, or general weakness should raise suspicion for infection. Headaches should raise suspicion for intracranial mass or encephalitis. A recent trauma involving facial fractures should raise suspicion for meningitis.


Medications are a common cause of AMS, particularly in older and vulnerable adults. A complete and accurate medication list should be obtained in all patients. It is important to note that medication lists obtained from a chart review or from triage are often inaccurate.[115,116] It may be necessary to call the patient's pharmacy to obtain an accurate medication list. Any recent changes or additions should be noted and the timing of symptoms should be compared with the change. Fill dates can also be compared with the number of pills present.

The American Geriatrics Society maintains a list of potentially inappropriate medications (Beers' criteria) in older adults.[117] Commonly used medications that can result in AMS include anticholinergic medications (antihistamines, antispasmodics, tricyclic antidepressants), benzodiazepines and nonbenzodiazepine hypnotics, and many skeletal muscle relaxants.[117]

Other rare causes of medication-induced AMS include antibiotics which can cause antibiomania. The exact pathophysiology is unknown, but clarithromycin, ciprofloxacin, and ofloxacin seem to be the most common causative agents. Though rare, it occurs among all age groups, with the greatest number of cases occurring in those in the 35-year-old group.[118] A key diagnostic feature is symptom onset soon after initiating the offending agent.[119] Cefepime has also been found to cause AMS. The mechanism is unknown but thought to be caused by Cefepime binding to GABA class A receptors resulting in increased central excitation.[120,121] Patients who are most susceptible appear to be those with conditions that compromise the integrity of the blood–brain barrier—inflammatory conditions, organic acid accumulation, renal dysfunction to name a few.[120,122,123] Metronidazole can also cause an encephalopathy, but the pathophysiology is thought to be separate than that of antibiomania and cefepime-induced AMS.[124]

Social History

Because drug overdoses and withdrawals are frequently a cause for AMS, a complete social history including substance use should be obtained. While this is a common problem for younger patients, older adults can also be abusers of ethanol and sedative hypnotics.[125,126] A sexual history should also be obtained, as high-risk sexual behavior can result in systemic infections or even neurosyphilis and HIV-related illnesses.

Medical/Surgical History

A patient's medical history may make them more prone to illnesses resulting in AMS. Prior CNS pathology, endocrine system disorders, and malignancies, among other causes, may make patients susceptible to AMS secondary to exacerbation of their disease processes or related processes (paraneoplastic syndromes). Similarly, a surgical history is important, as postsurgical complications such as infections may result in AMS.