Diagnosing Hyperosmolar Hyperglycemic State (HHS)
Immediately obtain plasma glucose, serum electrolytes with calculated anion gap, serum osmolality, blood urea nitrogen, creatinine, serum ketones, arterial blood gases, complete blood count with differential, urinalysis with urine ketones, electrocardiogram, and HbA1c upon suspicion of HHS in an older adult with type 2 diabetes. 1
Diagnostic Criteria
HHS is confirmed when all of the following metabolic thresholds are met:
- Blood glucose ≥600 mg/dL 1
- Effective serum osmolality ≥320 mOsm/kg H₂O, calculated as: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1
- Serum bicarbonate ≥15 mEq/L 1
- Arterial pH ≥7.30 1
- Small or absent ketones in urine and serum 1
Critical point: Mental status changes (ranging from lethargy to coma) are common but NOT required for diagnosis—patients meeting metabolic criteria warrant HHS management even if fully alert. 1, 2
Calculate Corrected Sodium
Add 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation above normal to assess true sodium status. 1
Identify Precipitating Factors
- Infection is the most common trigger—obtain bacterial cultures (blood, urine, throat) if suspected 1
- Consider acute cerebrovascular accident, myocardial infarction, or medications affecting carbohydrate metabolism 1
- Obtain chest X-ray if clinically indicated 1
Distinguish from Other Conditions
Starvation ketosis: Glucose rarely >250 mg/dL, bicarbonate usually not <18 mEq/L 1
Alcoholic ketoacidosis: Variable glucose (can be hypoglycemic to mildly elevated), profound acidosis possible 1
Diabetic ketoacidosis (DKA): Glucose >250 mg/dL, pH <7.3, bicarbonate <15 mEq/L, moderate ketonuria/ketonemia 3
Initial Management Steps
Immediate Triage and Monitoring
Admit to intensive care unit immediately—HHS patients have greater volume depletion (total body water deficit approximately 9 liters or 100-220 mL/kg) and are typically triggered by acute illness. 1, 4
Monitor serum osmolality regularly and aim to reduce osmolality by 3-8 mOsm/kg/h (not exceeding this rate to minimize risk of central pontine myelinolysis and other neurological complications). 1, 4, 5
Fluid Resuscitation
Begin isotonic 0.9% sodium chloride at 15-20 mL/kg/h during the first hour to restore circulating volume and tissue perfusion. 3, 4
Aim to correct estimated fluid deficits within 24 hours. 1
An initial rise in sodium level is expected and is not itself an indication for hypotonic fluids. 5
Insulin Administration
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. 1, 5
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). 1
Target glucose decline of 50-75 mg/dL/h. 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 is achieved. 1
Potassium Management
If serum potassium is <3.3 mEq/L, hold insulin and give potassium replacement until potassium is ≥3.3 mEq/L. 1
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)—total body potassium deficit in HHS is 5-15 mEq/kg. 1
Glucose Management During Treatment
Start glucose infusion (5% or 10%) once blood glucose <14 mmol/L (252 mg/dL) to prevent hypoglycemia while continuing insulin to normalize osmolality. 4
Target blood glucose of 10-15 mmol/L (180-270 mg/dL) in the first 24 hours. 4
Monitoring During Treatment
Draw blood every 2-4 hours for serum electrolytes, glucose, blood urea nitrogen, creatinine, and osmolality. 3
Monitor fluid input/output, blood pressure, heart rate, and clinical examination to assess hydration progress. 3
Venous pH is adequate for monitoring; repeat arterial blood gases are generally unnecessary. 3
Common Pitfalls to Avoid
Do not correct hyperglycemia or osmolality too rapidly—change in serum osmolality should not exceed 3-8 mOsm/kg/h to prevent osmotic demyelination syndrome. 1, 4
Do not administer bicarbonate—it does not improve outcomes in HHS. 3
Do not start insulin before adequate fluid resuscitation unless significant ketonaemia is present. 5
Monitor for complications including vascular occlusions (mesenteric artery occlusion, myocardial infarction), disseminated intravascular coagulopathy, rhabdomyolysis, cerebral edema, and venous thromboembolism. 4, 6
Resolution Criteria
HHS is resolved when: