Key Differences in Managing Hyperosmolar Hyperglycemic State (HHS) vs Diabetic Ketoacidosis (DKA)
The management of HHS requires more aggressive fluid replacement and less aggressive initial insulin therapy compared to DKA, reflecting their distinct pathophysiologies and clinical presentations. 1, 2
Diagnostic Criteria
- DKA: Blood glucose >250 mg/dL, arterial pH <7.3, bicarbonate <15 mEq/L, and moderate ketonuria or ketonemia 1, 3
- HHS: Blood glucose >600 mg/dL, arterial pH >7.3, bicarbonate >15 mEq/L, effective serum osmolality >320 mOsm/kg, and altered mental status or severe dehydration 1, 2
Fluid Therapy Differences
- HHS requires more aggressive fluid replacement due to greater dehydration (total body water deficit ~9 liters or 100-200 mL/kg) compared to DKA (total body water deficit ~6 liters) 1, 2
- Both conditions initially require isotonic saline (0.9% NaCl) at 15-20 mL/kg/h during the first hour 1, 3
- In HHS, fluid replacement should be carefully managed to avoid rapid changes in serum osmolality (not exceeding 3 mOsm/kg/h) to prevent central pontine myelinolysis 4
Insulin Therapy Differences
- In DKA: Begin insulin therapy immediately with IV bolus of regular insulin at 0.1-0.15 units/kg followed by continuous infusion at 0.1 unit/kg/h 1, 3
- In HHS: Delay insulin therapy until fluid resuscitation has begun and hypokalemia is excluded; insulin may be withheld until blood glucose stops falling with IV fluids alone 2, 4
- In DKA: Continue insulin until resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) even if blood glucose normalizes 1, 3
- In HHS: Continue insulin until mental status improves and hyperosmolarity resolves 2
Electrolyte Management
- Potassium deficits are typically greater in HHS (5-15 mEq/kg) compared to DKA (3-5 mEq/kg) 1, 2
- Both conditions require potassium replacement when serum levels fall below 5.5 mEq/L, aiming to maintain serum K+ between 4-5 mmol/L 1, 3
- Phosphate replacement (20-30 mEq/L potassium phosphate) may be considered in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL 2
Monitoring Parameters
- In DKA: Direct measurement of β-hydroxybutyrate in blood is preferred for monitoring ketone resolution 1
- Both conditions require monitoring of serum electrolytes, glucose, blood urea nitrogen, creatinine every 2-4 hours 1, 2
- In HHS: Regular calculation of serum osmolality is crucial to monitor treatment response, aiming to reduce osmolality by 3-8 mOsm/kg/h 4
Resolution Criteria
- DKA resolution: Glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, anion gap ≤12 mEq/L 1, 3
- HHS resolution: Normalized osmolality, improved mental status, and controlled blood glucose levels (250-300 mg/dL until hyperosmolarity resolves) 2
Transition to Subcutaneous Insulin
- For both conditions, basal insulin should be administered 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 5, 1
- Recent studies show that low-dose basal insulin analog given with IV insulin may prevent rebound hyperglycemia without increased hypoglycemia risk 5
Common Pitfalls and Complications
- In DKA: Premature termination of insulin therapy before complete resolution of ketosis can lead to recurrence 1
- In HHS: Rapid correction of hyperosmolality may lead to cerebral edema or central pontine myelinolysis 4, 6
- In both conditions: Inadequate fluid resuscitation and electrolyte replacement can worsen outcomes 1, 2
- In DKA: Bicarbonate administration is generally not recommended unless pH is <6.9 1, 2
Special Considerations
- HHS has a higher mortality rate than DKA and may be complicated by myocardial infarction, stroke, seizures, and cerebral edema 4
- In HHS, an initial rise in sodium level is expected and is not itself an indication for hypotonic fluids 4
- Both conditions require identification and treatment of precipitating causes (infection, myocardial infarction, stroke, medication non-compliance) 2, 3