What laboratory tests should be ordered for a patient presenting with altered mental status?

Laboratory Testing for Altered Mental Status

Order an immediate finger-stick glucose, complete blood count, comprehensive metabolic panel, and toxicology screen as your core initial workup, then add targeted tests based on clinical context—this approach identifies the vast majority of life-threatening and reversible causes. 1, 2

Immediate Point-of-Care Testing

• Perform finger-stick glucose immediately upon patient contact before any other testing, as hypoglycemia is rapidly reversible, potentially fatal if missed, and frequently mimics intoxication or withdrawal 1, 2
• If glucose is <70 mg/dL (<4 mmol/L), administer 30-50 g IV glucose urgently 1, 2
• If unable to check glucose and the patient has impaired mental state, presume hypoglycemia and give IV glucose empirically 1
• Never delay glucose testing to obtain neuroimaging first—even brief hypoglycemia causes permanent brain damage 2

Core Laboratory Panel (Order for All Patients)

Complete Blood Count (CBC) with differential to identify:

• Infection (leukocytosis/leukopenia) 2
• Anemia contributing to altered mental status 2
• Hematologic abnormalities 2

Comprehensive Metabolic Panel including: 2

• Electrolytes (sodium, potassium, chloride, bicarbonate)
• Renal function (BUN, creatinine)
• Hepatic panel (AST, ALT, bilirubin, alkaline phosphatase)
• Glucose (confirmatory after point-of-care)
• Calcium, magnesium, phosphate

Additional first-line tests:

• Thyroid-Stimulating Hormone (TSH)—thyroid dysfunction is a reversible cause 2
• Vitamin B12 level—deficiency causes cognitive impairment 2
• Urinalysis—to detect infection 2

Context-Specific Laboratory Testing

For suspected intoxication or substance use:

• Comprehensive toxicology screen (urine and serum) 2, 3
• Blood alcohol level 2
• Specific drug levels if indicated (acetaminophen, salicylates, anticonvulsants, lithium) 4

For patients with cirrhosis: 5

• Metabolic assessment for precipitating factors
• Drug and alcohol levels
• Do NOT routinely order ammonia levels—they are variable, unreliable, and elevated in non-hepatic encephalopathy conditions; however, a low ammonia level in a confused patient points away from hepatic encephalopathy 5

For suspected stroke or cardiovascular etiology: 2

• Coagulation studies (PT/INR, aPTT)
• Troponin
• 12-lead ECG

For respiratory concerns:

• Arterial blood gas 2

For women of childbearing age:

• Pregnancy test (urine or serum β-hCG) 2

For elderly patients or those with specific risk factors: 5

• Consider chest X-ray if pulmonary infection suspected
• ECG in geriatric patients
• HIV testing and syphilis serology (RPR/VDRL) based on risk factors 6

High-Yield Populations Requiring More Extensive Testing

Certain groups benefit from broader laboratory evaluation: 5, 6

• Age ≥65 years
• First episode of altered mental status
• Patients with substance abuse history
• Those who are disoriented or confused
• Lower socioeconomic status
• Abnormal vital signs (tachycardia, fever, hypertension, hypotension) 6
• Patients without prior psychiatric history presenting with confusion 6

What NOT to Order Routinely

Avoid reflexive extensive panels: 5, 6

• History and physical examination predict 83-98% of clinically significant abnormalities 6
• Routine testing yields only 1.4-1.8% clinically meaningful results not detected by history/physical 5
• False-positive tests are 8 times more common than true-positive results 5

Ammonia levels: 5

• Not recommended for routine diagnosis in cirrhotic patients
• Variable within patients and laboratories
• Elevated in non-hepatic encephalopathy conditions

Routine brain imaging: 5, 2

• Not warranted for recurrent, non-focal presentations similar to prior episodes
• Reserve for specific indications (see below)

When to Add Brain Imaging

Order CT or MRI brain selectively for: 5, 2

• First episode of altered mental status
• Focal neurological deficits or new focal neurological signs
• Recent head trauma
• New-onset seizures
• Signs of increased intracranial pressure
• Unsatisfactory response to treatment of precipitating factors
• Unsatisfactory response to empirical hepatic encephalopathy therapy (in cirrhotic patients)

Critical Diagnostic Pitfalls

• Never assume intoxication without excluding hypoglycemia first—the presentations overlap significantly and hypoglycemia causes irreversible brain injury 1, 2
• Never label patients with "withdrawal" or substance-induced symptoms before eliminating metabolic causes, particularly in high-risk groups 6
• Remember altered mental status is a diagnosis of exclusion—always investigate reversible causes including infections, medications, metabolic disturbances, and substance withdrawal 2
• Do not skip testing in patients with known psychiatric illness—they can still have medical causes for acute changes 5, 6

Practical Testing Algorithm

1. Immediate (within 5 minutes): Finger-stick glucose 1, 2
2. Stat labs (within 30 minutes): CBC, comprehensive metabolic panel, TSH, B12, urinalysis 2
3. Add based on history/exam: Toxicology screen, blood alcohol, specific drug levels, troponin, coagulation studies, pregnancy test 2, 4
4. Consider in high-risk patients: Chest X-ray, HIV, syphilis serology 5, 6
5. Reserve for specific indications: Brain imaging, lumbar puncture, EEG 5, 2

The most common etiologies identified are neurologic (28-35%), toxicologic (21-23%), infectious (9-10%), and endocrine/metabolic (5-8%), with mortality rates of 8-10% in this population. 3, 4 This targeted approach maximizes diagnostic yield while avoiding unnecessary testing that generates false positives and delays treatment.