What is the treatment for Hyperosmolar Hyperglycemic State (HHS)?

Treatment of Hyperosmolar Hyperglycemic State (HHS)

Begin immediate fluid resuscitation with 0.9% sodium chloride at 15-20 mL/kg/hour for the first hour to restore circulatory volume, followed by insulin therapy only after osmolality stops declining with fluids alone (unless significant ketonemia is present). 1, 2

Initial Assessment and Diagnostic Criteria

HHS is diagnosed by the following parameters:

• Marked hyperglycemia ≥30 mmol/L (≥540 mg/dL) 2
• Elevated serum osmolality ≥320 mOsm/kg (calculated as: [2×Na+] + glucose + urea) 2
• Minimal or absent ketones ≤3.0 mmol/L 2
• Minimal acidosis with pH >7.3 and bicarbonate ≥15 mmol/L 2
• Neurologic abnormalities, most commonly altered mental status ranging from confusion to coma 1, 3

Treatment Algorithm

Phase 1: Initial Resuscitation (0-60 minutes)

Fluid Resuscitation - The Priority:

• Administer 0.9% sodium chloride at 15-20 mL/kg/hour during the first hour to restore circulating volume and tissue perfusion 1, 2
• Typical total body water deficit is approximately 100-220 mL/kg (often 9-10 liters) 1, 2
• Fluid replacement alone will cause blood glucose to fall initially 4, 2

Critical Pitfall: Do NOT start insulin immediately. Early insulin administration before adequate fluid resuscitation may be detrimental and can precipitate vascular collapse 4, 2

Phase 2: Ongoing Fluid Management (1-24 hours)

• Continue 0.9% sodium chloride to correct estimated fluid deficits within 24 hours 1
• An initial rise in sodium is expected and normal - this is NOT an indication to switch to hypotonic fluids 4, 2
• Exercise caution in elderly patients due to risk of fluid overload 2
• Target urine output ≥0.5 mL/kg/hour as a marker of adequate rehydration 2

Phase 3: Insulin Therapy

Timing is Critical:

• Withhold insulin until blood glucose stops falling with IV fluids alone (unless significant ketonemia is present) 4, 2
• This typically occurs after initial fluid resuscitation is underway 2

Insulin Dosing:

• Administer IV bolus of regular insulin 0.1 units/kg body weight 1
• Follow with continuous infusion at 0.1 units/kg/hour 1, 2
• When glucose reaches 250-300 mg/dL (14 mmol/L), add 5-10% dextrose to IV fluids while continuing insulin infusion at a reduced rate 1, 5, 2
• Target blood glucose 10-15 mmol/L (180-270 mg/dL) in the first 24 hours - do not correct too rapidly 2

Rationale: Insulin is essential for reversing metabolic derangements, but premature administration before volume restoration can worsen hypotension and organ perfusion 4

Phase 4: Electrolyte Management

Potassium Replacement:

• Monitor potassium levels every 2-4 hours as insulin therapy drives potassium intracellularly and can cause life-threatening hypokalemia 1, 2
• Begin potassium replacement when serum levels fall below 5.5 mEq/L, assuming adequate urine output (≥0.5 mL/kg/hour) 1, 2
• Total body potassium deficits are common despite potentially normal or elevated initial levels due to dehydration 1

Other Electrolytes:

• Monitor and replace phosphate, magnesium as needed 2

Phase 5: Monitoring Parameters

Osmolality - The Most Critical Parameter:

• Calculate serum osmolality every 2-4 hours using: [2×Na+] + glucose + urea 2
• Target osmolality reduction of 3-8 mOsm/kg/hour 1, 4, 2
• Do NOT exceed this rate - rapid osmolality correction can precipitate cerebral edema and central pontine myelinolysis, which are potentially fatal complications 6, 4, 2

Laboratory Monitoring:

• Blood glucose every 2-4 hours 1, 2
• Serum electrolytes, BUN, creatinine, osmolality, and venous pH every 2-4 hours 1, 2

Clinical Monitoring:

• Vital signs hourly initially 2
• Neurologic status continuously 2
• Urine output hourly 2

Identifying and Treating Precipitating Causes

Most Common Precipitants:

• Infection is the most common trigger (pneumonia, urinary tract infection, sepsis) 1, 7
• Acute cardiovascular events (myocardial infarction, stroke) 1, 7
• Medication non-compliance or inadequate diabetes management 2
• Medications that worsen glycemic control (diuretics, corticosteroids, beta-blockers) 5

Action Required:

• Identify and treat any correctable underlying cause simultaneously with metabolic correction 1, 2
• Obtain cultures, imaging, and other diagnostics as clinically indicated 2

Resolution Criteria and Transition

HHS is Resolved When:

• Osmolality <300 mOsm/kg 2
• Hypovolemia corrected (urine output ≥0.5 mL/kg/hour) 2
• Cognitive status returned to baseline 2
• Blood glucose <15 mmol/L (270 mg/dL) 2

Transition from IV to Subcutaneous Insulin:

• Administer basal subcutaneous insulin 2-4 hours BEFORE stopping IV insulin to prevent rebound hyperglycemia 1

Important Note: Many patients with HHS will not require long-term insulin therapy and can be managed with oral agents or diet modification after recovery 5

Critical Complications to Prevent

Cerebral Edema:

• Rare but frequently fatal complication with 70% mortality once symptomatic 6
• Prevention requires gradual osmolality correction (maximum 3-8 mOsm/kg/hour) 6, 1, 2
• More common in children and young adults but can occur at any age 6, 1

Central Pontine Myelinolysis:

• Associated with rapid changes in osmolality during treatment 4, 2
• Prevented by adhering to gradual osmolality correction targets 4, 2

Thromboembolism:

• HHS creates a hypercoagulable state 2
• VTE prophylaxis should be implemented 2

Level of Care

• Patients require intensive care unit admission due to critical illness and need for frequent monitoring 3, 2
• Involve diabetes specialist team as soon as possible 4, 2
• Nurse in areas where staff are experienced in HHS management 4, 2

Key Differences from DKA

HHS differs fundamentally from diabetic ketoacidosis:

• HHS develops over days (vs. hours for DKA) 4
• Dehydration and metabolic disturbances are more extreme 4
• Higher mortality rate than DKA 4, 2
• Fluid resuscitation takes precedence over insulin (opposite priority from DKA) 4, 2