Diagnostic Criteria for Hyperosmolar Hyperglycemic State (HHS)
HHS is diagnosed when blood glucose is ≥600 mg/dL, effective serum osmolality is ≥320 mOsm/kg H₂O, arterial pH is ≥7.30, serum bicarbonate is ≥15 mEq/L, and ketones are minimal or absent in urine and serum. 1, 2
Essential Laboratory Evaluation
Upon suspicion of HHS, immediately obtain the following:
- Plasma glucose, serum electrolytes with calculated anion gap, and serum osmolality 1
- Blood urea nitrogen, creatinine, serum ketones, arterial blood gases 1
- Complete blood count with differential, urinalysis with urine ketones by dipstick 1
- Electrocardiogram and HbA1c 1
- Bacterial cultures (blood, urine, throat) if infection suspected, and chest X-ray if clinically indicated 1
Critical Calculation
Calculate effective serum osmolality as: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 3, 1, 2
Correct serum sodium for hyperglycemia by adding 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation above normal 3, 1
Clinical Presentation Characteristics
- HHS develops over days to a week, unlike DKA which develops over hours to days 3
- Change in cognitive state is common, ranging from full alertness to profound lethargy or coma 3, 1
- The degree of mental obtundation typically correlates with severity of hyperosmolarity 1
- Patients often present with copresenting acute illness 3
- Polyuria, polydipsia, weight loss, and dehydration are typical features 3
Important Diagnostic Consideration
Altered mental status is NOT mandatory for HHS diagnosis—patients meeting metabolic thresholds (glucose ≥600 mg/dL, osmolality ≥320 mOsm/kg) warrant HHS management regardless of alertness. 1 This is a critical pitfall to avoid, as clinicians may mistakenly exclude HHS in alert patients.
Differential Diagnosis
Distinguish HHS from starvation ketosis (glucose rarely >250 mg/dL, bicarbonate usually not <18 mEq/L) and alcoholic ketoacidosis (variable glucose, can be hypoglycemic to mildly elevated, profound acidosis possible). 1
One-third of hyperglycemic emergencies have a hybrid DKA-HHS presentation. 3
Common Precipitating Factors
Infection is the most common precipitant of HHS, followed by acute cerebrovascular accident, myocardial infarction, and medications affecting carbohydrate metabolism. 1, 4
Treatment of Hyperosmolar Hyperglycemic State (HHS)
Individuals with suspected HHS should be immediately evaluated and treated in the inpatient setting, preferably in an intensive care unit, due to greater volume depletion and typical triggering by acute illness. 3, 2
Fluid Resuscitation (First Priority)
Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/h (1-1.5 L in average adult) during the first hour to restore circulatory volume and renal perfusion. 2, 5
- Total body water deficit in HHS is approximately 9 liters (100-220 mL/kg) 2, 5
- Aim to correct estimated fluid deficits within 24 hours 3, 2
- The induced change in serum osmolality should not exceed 3-8 mOsm/kg/h to minimize risk of neurological complications including central pontine myelinolysis 3, 6, 5
Subsequent Fluid Management
After initial volume restoration, continue with 0.9% NaCl or switch to 0.45% NaCl based on hydration state, serum electrolytes, and urine output. 2, 7
When plasma glucose reaches 300 mg/dL, add 5% or 10% dextrose to intravenous fluids. 3, 5
Insulin Therapy (Critical Timing)
Withhold insulin until blood glucose level is no longer falling with IV fluids alone, unless ketonaemia is present—early use of insulin before adequate fluid resuscitation may be detrimental. 6, 5 This represents a key difference from DKA management.
Once indicated, initiate with IV bolus of regular insulin at 0.15 units/kg body weight, followed by continuous infusion at 0.1 unit/kg/h (5-7 units/h in adults). 3, 2
- Plasma glucose should decrease at a rate of 50-75 mg/dL/h 3
- If plasma glucose does not fall by 50 mg/dL from initial value in the first hour, check hydration status; if acceptable, double insulin infusion every hour until steady glucose decline of 50-75 mg/h is achieved 3
- When plasma glucose reaches 300 mg/dL, decrease insulin infusion to 0.05-0.1 units/kg/h (3-6 units/h) 2
Potassium Replacement
Once renal function is assured and serum potassium is known, add potassium to IV fluids at 20-30 mEq/L (2/3 KCl and 1/3 KPO₄). 3, 2
Total body potassium deficit in HHS is 5-15 mEq/kg and requires close monitoring. 2
If serum potassium is <3.3 mEq/L, hold insulin and give potassium replacement until potassium is ≥3.3 mEq/L. 3
Monitoring During Treatment
Check blood glucose every 1-2 hours until stable. 2
Monitor serum electrolytes, blood urea nitrogen, creatinine, and calculated osmolality every 2-4 hours. 2
Assess fluid input/output, vital signs, and mental status frequently. 2
Monitor serum osmolality regularly to ensure it decreases by 3-8 mOsm/kg/h, not just individual components. 1, 5
Transition to Subcutaneous Insulin
Administer basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia. 2
Recent studies show that low-dose basal insulin analog given with IV insulin may prevent rebound hyperglycemia. 2
Treatment of Underlying Causes
Identify and treat underlying causes, especially infections, as appropriate management of precipitating illnesses helps reduce the high mortality associated with HHS. 2, 7, 4
Bicarbonate administration is generally not recommended. 2
Resolution Criteria
HHS is resolved when osmolality is <300 mOsm/kg, hypovolaemia is corrected (urine output ≥0.5 mL/kg/h), cognitive status has returned to pre-morbid state, and blood glucose is <15 mmol/L (<270 mg/dL). 5
Critical Pitfalls to Avoid
Rapid changes in osmolality during treatment may precipitate central pontine myelinolysis—aim for gradual correction. 6, 5
An initial rise in sodium level is expected and is not itself an indication for hypotonic fluids. 6
Patients should be nursed in areas where staff are experienced in HHS management, and the diabetes specialist team should be involved as soon as possible. 6