Blood Glucose Target During HHS Treatment
Target blood glucose between 200–250 mg/dL until resolution of hyperosmolar hyperglycemic state, then maintain between 250–300 mg/dL during the first 24 hours to prevent overly rapid osmolality decline. 1
Primary Glucose Targets in HHS
The glucose management strategy in HHS differs fundamentally from DKA because the priority is controlled reduction of osmolality rather than rapid glucose normalization:
Keep glucose between 200–250 mg/dL until HHS resolution (defined as osmolality <300 mOsm/kg, corrected hypovolemia, and return to baseline mental status). 1
During the first 24 hours, maintain glucose at 250–300 mg/dL to limit osmolality reduction to the safe range of 3–8 mOsm/kg/h and minimize risk of cerebral edema and central pontine myelinolysis. 2, 3
Target glucose decline of 50–75 mg/dL per hour once insulin is initiated, but this rate should be achieved primarily through fluid resuscitation rather than aggressive insulin dosing. 2
Critical Timing: When to Add Dextrose
Add 5% or 10% dextrose to IV fluids when plasma glucose reaches 250–300 mg/dL while continuing insulin infusion at a reduced rate of 0.05–0.1 units/kg/h. 2, 4 This prevents overly rapid glucose decline that can precipitate dangerous osmotic shifts. 2
The most common error is adding dextrose too early, which delays correction of hyperosmolarity and prolongs altered mental status. 2
Why HHS Targets Are Higher Than DKA
The 2025 ADA guidelines explicitly differentiate targets: DKA requires glucose 150–200 mg/dL until resolution, whereas HHS requires 200–250 mg/dL. 1 This reflects three key differences:
HHS patients have more severe hyperosmolarity (≥320 mOsm/kg vs. variable in DKA), making rapid osmolality correction dangerous. 2
Neurological complications are more common in HHS, with mortality up to 15% compared to <1% in DKA. 2, 3
Fluid replacement alone causes significant glucose decline in HHS, so insulin should be withheld until glucose stops falling with IV fluids alone (unless ketonemia is present). 5, 3
Insulin Management Specific to HHS
Delay insulin initiation until blood glucose is no longer falling with IV fluid administration alone, unless ketonemia (≥3.0 mmol/L) is present. 2, 5, 3
Start with IV bolus of 0.1–0.15 units/kg regular insulin, followed by continuous infusion at 0.1 units/kg/h. 2, 6
Reduce insulin infusion to 0.05–0.1 units/kg/h once dextrose is added at glucose 250–300 mg/dL. 2, 4
Monitoring Requirements
Check blood glucose every 2–4 hours along with serum electrolytes, osmolality, and venous pH until stable. 1, 2
Calculate effective osmolality as 2[Na (mEq/L)] + glucose (mg/dL)/18 to guide therapy; aim for reduction of 3–8 mOsm/kg/h. 2, 3
Correct serum sodium for hyperglycemia by adding 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL to assess true sodium status. 2
Resolution Criteria
HHS is considered resolved when all of the following are met: 3
- Osmolality <300 mOsm/kg
- Hypovolemia corrected (urine output ≥0.5 mL/kg/h)
- Cognitive status returned to pre-morbid baseline
- Blood glucose <15 mmol/L (270 mg/dL)
Common Pitfalls to Avoid
Never target euglycemia during acute HHS treatment—this causes dangerous osmotic shifts and increases mortality. 2, 3
Do not start insulin before adequate fluid resuscitation unless significant ketonemia is present; early insulin use may be detrimental. 5, 3
Avoid rapid glucose decline below 250 mg/dL in the first 12–24 hours, as this correlates with increased risk of cerebral edema and central pontine myelinolysis. 2, 3
Monitor for rebound hyperglycemia when transitioning from IV to subcutaneous insulin; administer basal insulin 2–4 hours before stopping the IV infusion. 4