Laboratory Tests for Evaluating Lethargy
The initial laboratory evaluation of a patient with lethargy should include complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, fasting blood glucose (glycohemoglobin), liver function tests, and thyroid-stimulating hormone. 1
Core Laboratory Tests
When evaluating a patient with lethargy, the following tests should be ordered:
First-line Tests (Essential)
- Complete blood count (CBC) with differential
- Comprehensive metabolic panel including:
- Electrolytes (sodium, potassium, chloride, bicarbonate)
- Calcium and magnesium
- Blood urea nitrogen (BUN)
- Serum creatinine
- Fasting blood glucose/glycohemoglobin
- Liver function tests (AST, ALT, alkaline phosphatase, bilirubin)
- Thyroid-stimulating hormone (TSH)
- Urinalysis
Second-line Tests (Based on Clinical Suspicion)
- Blood cultures (if infection suspected)
- Arterial blood gas (if hypoxia or acid-base disturbance suspected)
- Toxicology screen
- Blood alcohol level
- Electrocardiogram (ECG)
- Chest radiograph (if respiratory or cardiac cause suspected)
Specific Clinical Scenarios
For Suspected Metabolic Causes
- Serum osmolality
- Ammonia level
- Lactic acid
- Ketones (serum and urine)
For Suspected Infectious Causes
- Blood cultures
- Prothrombin time/international normalized ratio (INR)
- Activated partial thromboplastin time (aPTT)
- C-reactive protein or erythrocyte sedimentation rate
- Lumbar puncture if meningitis suspected 1
For Suspected Endocrine Causes
- Free T4 (in addition to TSH)
- Cortisol level
- Glucose monitoring 1
Special Considerations
Pediatric Patients
In pediatric patients with lethargy, additional considerations include:
- Evaluation for intussusception if gastrointestinal symptoms are present 2
- Screening for congenital metabolic disorders
- Evaluation for diabetic ketoacidosis (DKA) with urine ketones 3
Elderly Patients
In elderly patients, consider:
- Medication levels (especially sedatives, opioids)
- Vitamin B12 and folate levels
- Ammonia level (if liver disease suspected)
Interpreting Results
- Hyponatremia, hyperkalemia, and metabolic acidosis with lethargy may indicate adrenal insufficiency
- Hyperglycemia with lethargy may indicate diabetic ketoacidosis
- Elevated liver enzymes with lethargy may indicate hepatic encephalopathy
- Abnormal TSH and free T4 may indicate thyroid dysfunction causing lethargy
Common Pitfalls to Avoid
- Failing to check glucose immediately - Hypoglycemia can cause lethargy and requires urgent treatment
- Overlooking electrolyte abnormalities - Particularly sodium, which can cause altered mental status
- Missing sepsis - Lethargy may be the presenting symptom of sepsis, especially in elderly or immunocompromised patients
- Neglecting medication effects - Always review current medications that could cause lethargy
- Focusing only on common causes - Consider rare but serious causes like meningitis or encephalitis in appropriate clinical contexts
By systematically evaluating these laboratory parameters, clinicians can identify the underlying cause of lethargy and implement appropriate treatment strategies to improve patient outcomes.