Laboratory Workup for Blood Glucose >500 mg/dL
When a patient presents with severe hyperglycemia (BG >500 mg/dL), immediately obtain arterial blood gases, complete blood count with differential, comprehensive metabolic panel (electrolytes, BUN, creatinine), calculated anion gap, serum or urine ketones (preferably β-hydroxybutyrate), urinalysis, and serum osmolality to differentiate between diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) and identify precipitating factors. 1, 2
Essential Immediate Laboratory Tests
Core Metabolic Assessment
- Arterial blood gases: Document pH and assess for metabolic acidosis (pH <7.3 suggests DKA) 1, 2
- Serum electrolytes with calculated anion gap: Identify high anion gap metabolic acidosis and guide potassium replacement 1, 2
- Serum bicarbonate: Levels ≤15-18 mEq/L indicate DKA; levels >15 mEq/L suggest HHS 1, 2
- Blood urea nitrogen and creatinine: Assess renal function, hydration status, and severity of dehydration 1, 2
- Serum osmolality calculation: Use formula 2[measured Na (mEq/L)] + glucose (mg/dL)/18; effective osmolality >320 mOsm/kg indicates HHS 1
Ketone Assessment
- Serum β-hydroxybutyrate (preferred) or serum ketones: This is the predominant and strongest ketone in DKA 1, 2
- Urinalysis with urine ketones: Provides supporting evidence but should not be used alone for diagnosis 2
- Critical pitfall: Do NOT use nitroprusside-based ketone tests for monitoring treatment response, as they only measure acetoacetic acid and acetone, not β-hydroxybutyrate, and may falsely suggest worsening ketosis during treatment 1, 2
Additional Essential Tests
- Complete blood count with differential: Evaluate for underlying infection as a precipitating factor 1, 2
- Corrected serum sodium: For each 100 mg/dL glucose >100 mg/dL, add 1.6 mEq to sodium value for corrected serum value 1
Secondary Laboratory Evaluation
Identify Precipitating Factors
- Electrocardiogram: Assess for myocardial ischemia or infarction as a precipitating cause 1
- Chest X-ray and cultures: Obtain as needed to identify infection 1
- Liver function tests: Evaluate hepatic function and potential complications 1
- Lipid profile: Assess for dyslipidemia associated with metabolic derangements 1, 3
- Thyroid-stimulating hormone: Exclude thyroid dysfunction as a precipitating or contributing factor 1, 3
Monitoring During Treatment
- Repeat serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH every 2-4 hours during active treatment 1
- Venous pH (usually 0.03 units lower than arterial pH) and anion gap can be followed to monitor resolution of acidosis without repeated arterial blood gases 1
Key Clinical Distinctions
DKA vs. HHS Differentiation
- DKA: Glucose typically >250 mg/dL, pH <7.3, bicarbonate ≤15-18 mEq/L, positive ketones, effective osmolality variable 1, 2
- HHS: Glucose >600 mg/dL, pH >7.3, bicarbonate >15 mEq/L, mild or absent ketonuria, effective osmolality >320 mOsm/kg 1
Critical Potassium Management
- Check serum potassium before initiating insulin therapy: If K+ <3.3 mEq/L, hold insulin and replace potassium first to avoid life-threatening hypokalemia 1
- Once renal function is confirmed and potassium is known, add 20-40 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO4) 1
Common Pitfalls to Avoid
- Do not rely on urine ketones alone for diagnosis or monitoring, as they are unreliable indicators of treatment response 2
- Do not use nitroprusside-based ketone assays for monitoring, as β-hydroxybutyrate converts to acetoacetic acid during treatment, falsely suggesting worsening ketosis 1, 2
- Always correct sodium for hyperglycemia to accurately assess volume status and avoid inappropriate fluid management 1
- Monitor for infection aggressively, as it is the most common precipitating factor for hyperglycemic crises 1, 4