Diagnosing Hyperosmolar Hyperglycemia
To diagnose hyperosmolar hyperglycemia (HHS), laboratory evaluation must include plasma glucose >600 mg/dL, effective serum osmolality >320 mOsm/kg, minimal or absent ketones, and altered mental status. 1, 2
Diagnostic Criteria
The American Diabetes Association defines HHS with the following criteria:
- Plasma glucose ≥600 mg/dL
- Arterial pH >7.30
- Serum bicarbonate >15 mEq/L
- Effective serum osmolality ≥320 mOsm/kg
- Small or absent urine and serum ketones
- Altered mental status (stupor/coma)
- Anion gap: variable 1
Required Laboratory Tests
Initial laboratory evaluation should include:
- Plasma glucose
- Blood urea nitrogen/creatinine
- Serum ketones
- Electrolytes (with calculated anion gap)
- Serum osmolality (measured or calculated)
- Urinalysis and urine ketones by dipstick
- Arterial blood gases
- Complete blood count with differential
- Electrocardiogram 1, 2
Calculation of Effective Serum Osmolality
Effective serum osmolality should be calculated using the formula:
- 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1
Sodium Correction
Sodium level should be corrected for hyperglycemia:
- Add 1.6 mEq to the sodium value for every 100 mg/dL of glucose >100 mg/dL 2
Clinical Assessment
Mental status evaluation is crucial as altered consciousness ranging from drowsiness to coma is a hallmark of HHS. Physical examination should assess:
- Vital signs (particularly for hypotension, tachycardia)
- Signs of dehydration (dry mucous membranes, poor skin turgor)
- Neurological status (ranging from lethargy to coma)
- Temperature (patients may be normothermic or hypothermic despite infection) 1
Differential Diagnosis
HHS must be distinguished from:
- Diabetic ketoacidosis (DKA) - differs by having significant ketosis and acidosis
- Starvation ketosis
- Alcoholic ketoacidosis
- Other causes of altered mental status 1
Common Pitfalls to Avoid
- Failing to calculate corrected sodium and effective osmolality: These are essential for diagnosis and monitoring treatment
- Overlooking precipitating factors: Always search for underlying infection, medication effects (corticosteroids, thiazides, sympathomimetics), cerebrovascular events, or substance abuse 1, 2
- Confusing HHS with DKA: HHS has higher glucose levels, higher osmolality, minimal ketosis, and often more profound dehydration 1
- Missing new-onset diabetes: HHS may be the first manifestation of diabetes, especially in elderly patients 1
Monitoring During Treatment
Once diagnosed, frequent monitoring is essential:
- Glucose and electrolytes every 2-4 hours
- Calculated osmolality regularly (should not decrease by more than 3 mOsm/kg/hour)
- Continuous assessment of mental status, vital signs, and fluid balance 2
Remember that HHS carries a higher mortality rate than DKA and requires careful management of fluid replacement and gradual correction of hyperglycemia and hyperosmolality to prevent complications such as cerebral edema and central pontine myelinolysis 3.
Key Differences from DKA
| Parameter | HHS | DKA |
|---|---|---|
| Glucose | ≥600 mg/dL | ≥250 mg/dL |
| Osmolality | ≥320 mOsm/kg | Variable |
| Ketones | Minimal/absent | Significant |
| pH | >7.30 | ≤7.30 |
| Bicarbonate | >15 mEq/L | ≤18 mEq/L |
| Mental status | Often severely altered | Variable |