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

Laboratory Evaluation

As with any complaint, the history and physical exam should guide laboratory testing. In patients who are unable to provide a history, a broad approach may be necessary. All patients presenting to the ED with AMS should have a fingerstick glucose performed as part of the primary survey to rule out hypoglycemia, which can be reversed immediately.

Complete Blood Count

A complete blood count may reveal profound anemia, thrombocytopenia, polycythemia, or thrombocytosis resulting in inadequate perfusion or hyperviscosity. A leukocytosis or leukopenia may be the result of a malignancy, infection, or an immunocompromised state. Thrombocytopenia may result in a spontaneous intracranial hemorrhage. Thrombocytosis may suggest an infectious etiology or malignancy.

Basic Metabolic Profile

A basic metabolic profile (serum sodium, potassium, chloride, bicarbonate, blood urea nitrogen, and creatinine) can evaluate for electrolyte or other blood chemistry abnormalities. An ionized calcium should be obtained to evaluate for hyperparathyroidism, hypercalcemia of malignancy, or for conditions associated with a low calcium based on their basic metabolic panel.[128] In malnourished patients or those with liver disease who have an abnormal serum calcium level, an albumin should be ordered to calculate a corrected calcium level.

Liver Function Tests

Liver function tests may reveal evidence of liver disease, but normal liver enzymes do not rule out disease. Liver disease may be intrinsic (e.g., cirrhosis of the liver, primary sclerosing cholangitis) or extrinsic (e.g., toxins, infection) in nature. Elevated alkaline phosphatase may represent evidence of gallbladder disease, but is nonspecific and may represent bone breakdown. If stigmata of liver disease is present (e.g., jaundice, musky odor, varicosities, ascites), an ammonia level should be considered. While an ammonia level should not be used for screening, it may be helpful for trending when being treated for hepatic encephalopathy.[129] Cholangitis may present with AMS along with right upper quadrant pain, jaundice, fever, and shock, known as Reynold's pentad.[130]


A lipase should be considered in patients with upper quadrant or midepigastric abdominal pain. Severe acute pancreatitis can even lead to pancreatic encephalopathy, a rare but poorly understood complication of acute pancreatitis.[131]

Endocrine Studies

Thyroid function tests (thyroid-stimulating hormone and free T4) should be considered in patients with signs and symptoms of hypothyroidism or hyperthyroidism. As mentioned earlier, it is important to consider hypothyroidism in elderly patients with unexplained vague symptoms, as these symptoms are often attributed to the normal aging process.[67]

A random cortisol should be considered in patients with signs and symptoms of adrenal insufficiency such as refractory shock, hyperkalemia with hyponatremia, and bronze-colored skin. Though far from a definitive test, a random cortisol level may help with the diagnosis.


A urinalysis should be considered in patients with AMS, particularly in elderly patients. Results, however, should be interpreted carefully as asymptomatic bacteriuria is common among all age groups and is frequently overtreated.[132] It is important for providers to not anchor on a urinary tract infection given the high rate of asymptomatic bacteriuria. In addition to evaluating for infection, a urinalysis can help determine hydration status based on the specific gravity and the presence/absence of ketones. It may also show evidence of myoglobinuria, which can represent hemolysis or rhabdomyolysis.

Toxicologic Evaluation

Like urinalyses, a urine drug screen (UDS) should be interpreted with caution. Though quick and easy to obtain, they are prone to both false positives and false negatives. They rely on multiple factors for detection and the time from ingestion to detection varies significantly.[133] It is important to note that it is often not the drug itself but a metabolite of the drug that is detected on a UDS.

In patients with a toxic overdose in which the substance is unknown or if concern for polysubstance ingestion is present, a serum osmolality should be drawn to calculate an osmolar gap to evaluate for toxic alcohols. Serum acetaminophen and salicylate levels should be considered in this patient population as well.

Lumbar Puncture

A lumbar puncture can evaluate for several etiologies of AMS, including subarachnoid hemorrhage, meningitis, and encephalitis. A lumbar puncture should be considered in all patients with AMS in whom no other etiology has been discovered or if they are immunocompromised. It should also strongly be considered in patients with a first-time psychosis if any atypical features are present. Prior to a lumbar puncture, a head CT should be performed on patients with AMS due to potential risk of iatrogenic herniation if increased intracranial pressure is present.[134]

The basic evaluation of cerebrospinal fluid (CSF) should include a total white blood cell count, protein, glucose, and culture. If concerns for other processes (e.g., Lyme disease, neurosyphilis, cryptococcal meningitis, anti-NMDA [N-methyl-aspartate] encephalitis, etc.) exist, specific antigens should be sent. We also recommend drawing an additional 3 to 4 mL of CSF to freeze in the event that further testing is needed after admission.