What are the symptoms and treatment of Hyperosmolar Hyperglycemic State (HHS)?

Symptoms of Hyperosmolar Hyperglycemic State (HHS)

HHS presents with profound dehydration, severe hyperglycemia (≥600 mg/dL), marked hyperosmolarity (≥320 mOsm/kg), and altered mental status ranging from lethargy to coma, developing gradually over days rather than hours. 1, 2

Clinical Presentation

Metabolic Features

• Blood glucose ≥600 mg/dL is the diagnostic threshold, significantly higher than DKA 1
• Effective serum osmolality ≥320 mOsm/kg H₂O, calculated as 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1
• Minimal or absent ketones in urine and serum (distinguishing feature from DKA) 1, 3
• Arterial pH ≥7.30 and serum bicarbonate ≥15 mEq/L (no significant acidosis) 1

Neurological Symptoms

• Mental status changes are the hallmark, with severity correlating directly with degree of hyperosmolarity 1, 2
• Presentation ranges from full alertness to profound lethargy, stupor, or coma 1
• Altered consciousness is more frequent in HHS than DKA 1
• Seizures may occur as a complication 4, 5

Important caveat: The absence of altered mental status does not exclude HHS diagnosis when metabolic criteria are met (glucose ≥600 mg/dL, osmolality ≥320 mOsm/kg) 1

Dehydration Signs

• Profound dehydration with fluid losses averaging 100-220 ml/kg body weight 5
• Marked hypovolemia requiring intensive fluid replacement 5
• Physical examination reveals severe volume depletion 3
• Recent polyuria and weight loss are common preceding symptoms 6

Temporal Pattern

• HHS develops over many days, contrasting with DKA which presents within hours 4
• The prolonged osmotic diuresis phase leads to severe depletion of both intracellular and extracellular fluid volumes 7

Treatment Approach

Fluid Resuscitation (Primary Intervention)

• 0.9% sodium chloride is the principal fluid for restoring circulating volume and reversing dehydration 4, 5
• Adults require an average of 9 L of 0.9% saline over 48 hours 3
• Aim to reduce osmolality by 3-8 mOsm/kg/h to minimize risk of neurological complications including central pontine myelinolysis 4, 5
• An initial rise in sodium level is expected and not itself an indication for hypotonic fluids 4

Insulin Administration (Delayed Compared to DKA)

• Withhold insulin until blood glucose is no longer falling with IV fluids alone (unless ketonaemia present) 4, 5
• Fluid replacement alone will cause a fall in blood glucose level 4
• Early use of insulin before adequate fluid resuscitation may be detrimental 4
• Once indicated, adults receive 0.1 units/kg IV bolus followed by 0.1 units/kg/hour continuous infusion until glucose <300 mg/dL 3
• Start 5% or 10% glucose infusion once blood glucose reaches 250-300 mg/dL and maintain this level until hyperosmolarity and mental status improve 8, 5

Electrolyte Management

• Potassium replacement should begin after urine output is established 3
• Corrected serum sodium should be calculated by adding 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation 1
• Monitor and replace other electrolytes as depleted 7

Monitoring Requirements

• Measure or calculate serum osmolality regularly to monitor treatment response 4, 5
• Intensive monitoring of glucose, sodium, and potassium levels is critical 3
• Monitor for complications including hypoglycemia, hypokalemia, and fluid overload 5

Critical Care Considerations

• Patients should be nursed in areas where staff are experienced in HHS management, typically ICU settings 4, 2
• Diabetes specialist team involvement should occur as soon as possible 4
• HHS has higher mortality than DKA (up to 70% with cerebral edema complications) 8, 4

Pediatric Modifications

• In children and adolescents, correct dehydration at a rate no more than 3 mOsm/hour to avoid cerebral edema 3
• HHS is increasingly affecting younger adults and children with type 2 diabetes 5

Precipitating Factors to Address

• Infection is the most common precipitant and must be identified and treated 1, 3
• Other triggers include acute cerebrovascular accident, myocardial infarction, stroke, and medications affecting carbohydrate metabolism 1
• Obtain bacterial cultures (blood, urine, throat) if infection suspected and chest X-ray if clinically indicated 1

Resolution Criteria

• Osmolality <300 mOsm/kg 5
• Hypovolemia corrected (urine output ≥0.5 ml/kg/h) 5
• Cognitive status returned to pre-morbid state 5
• Blood glucose <15 mmol/L (270 mg/dL) 5