What is the recommended management of hyperosmolar hyperglycemic state (HHS)?

Management of Hyperosmolar Hyperglycemic State (HHS)

Begin aggressive fluid resuscitation with 0.9% saline at 15-20 mL/kg/h in the first hour, and delay insulin administration until blood glucose stops falling with IV fluids alone (unless ketonemia is present), as fluid replacement is the cornerstone of HHS management and premature insulin use may be detrimental. 1, 2

Initial Assessment and Diagnosis

Diagnostic Criteria:

• Blood glucose ≥600 mg/dL 1, 3
• Effective serum osmolality ≥320 mOsm/kg (calculated as: 2[measured Na] + glucose/18) 1, 3
• Arterial pH ≥7.30 1, 3
• Serum bicarbonate ≥15 mEq/L 1, 3
• Small or absent ketones (β-hydroxybutyrate ≤3.0 mmol/L) 1, 3
• Altered mental status or severe dehydration (though altered mental status is not mandatory for diagnosis if metabolic criteria are met) 3

Immediate Laboratory Tests:

• Plasma glucose, serum electrolytes with calculated anion gap, serum osmolality 3
• Blood urea nitrogen, creatinine, arterial blood gases 3
• Complete blood count with differential, urinalysis with urine ketones 3
• Electrocardiogram, HbA1c 3
• Bacterial cultures (blood, urine, throat) if infection suspected 3
• Chest X-ray if pneumonia suspected 3

Corrected Sodium Calculation:

• Add 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation above 100 mg/dL 1, 3

Fluid Resuscitation Strategy

Phase 1 (First Hour):

• Administer 0.9% saline at 15-20 mL/kg/h (1-1.5 L in average adult) to restore circulatory volume 1, 4
• Total body water deficit is approximately 9 liters (100-220 mL/kg) 1, 3

Phase 2 (After First Hour):

• If corrected sodium is normal or elevated: switch to 0.45% saline at 4-14 mL/kg/h 1
• If corrected sodium is low: continue 0.9% saline at 4-14 mL/kg/h 1
• Aim to correct estimated fluid deficits within 24 hours 1, 3

Critical Target:

• Reduce osmolality by 3-8 mOsm/kg/h (never exceed this rate to prevent cerebral edema and central pontine myelinolysis) 1, 3, 2, 5

Special Populations:

• Elderly patients and those with renal/cardiac compromise require frequent assessment to avoid fluid overload 1
• Pediatric patients: 0.9% saline at 10-20 mL/kg/h first hour (not exceeding 50 mL/kg over first 4 hours), then replace deficit evenly over 48 hours using 0.45-0.9% saline at 1.5 times maintenance 1

Insulin Therapy

Timing is Critical:

• Withhold insulin until blood glucose stops falling with IV fluids alone, unless ketonemia is present 1, 3, 2
• Early insulin use before adequate fluid resuscitation may be detrimental 2

Dosing Protocol (Adults):

• IV bolus: 0.15 units/kg body weight 1, 3
• Continuous infusion: 0.1 unit/kg/h (5-7 units/h) 1, 3
• Target glucose decline: 50-75 mg/dL/h 3
• If glucose does not fall by 50 mg/dL in first hour: check hydration status, then double insulin infusion hourly until steady decline achieved 3

Glucose Management:

• When plasma glucose reaches 250-300 mg/dL: reduce insulin to 0.05-0.1 units/kg/h 1, 3
• Add 5% or 10% dextrose to 0.45% saline when glucose reaches 250-300 mg/dL 3, 4
• Maintain glucose at 250-300 mg/dL until hyperosmolarity and mental status improve 3, 4

Pediatric Dosing:

• Continuous infusion at 0.1 unit/kg/h without initial bolus 1

Potassium Management

Critical Safety Point:

• If serum potassium <3.3 mEq/L: hold insulin and give potassium replacement until potassium ≥3.3 mEq/L 3
• Insulin drives potassium intracellularly and can precipitate life-threatening hypokalemia 3

Replacement Protocol:

• Total body potassium deficit: 5-15 mEq/kg 1, 3
• Once renal function assured and potassium known: add 20-30 mEq/L to IV fluids (2/3 KCl and 1/3 KPO₄) 1, 3

Phosphate Replacement:

• Consider 20-30 mEq/L potassium phosphate if: cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL 3, 4
• Avoid overzealous phosphate therapy (can cause severe hypocalcemia) 3

Monitoring Requirements

Frequent Laboratory Monitoring:

• Blood glucose: every 1-2 hours until stable 1
• Serum electrolytes, BUN, creatinine, calculated osmolality: every 2-4 hours 1, 3, 4
• Venous pH adequate (repeat arterial blood gases generally unnecessary) 3

Clinical Monitoring:

• Fluid input/output, vital signs, mental status: assess frequently 1
• Monitor for signs of cerebral edema: lethargy, behavioral changes, seizures, incontinence, pupillary changes, bradycardia, respiratory arrest 4

Transition to Subcutaneous Insulin

Preventing Rebound Hyperglycemia:

• Administer basal subcutaneous insulin 2-4 hours before stopping IV insulin 1, 3, 4
• This overlap is essential to prevent recurrence of hyperglycemic crisis 3

Treatment of Precipitating Causes

Most Common Precipitants:

• Infection (most common): obtain cultures and administer appropriate antibiotics 6, 3, 4
• Other causes: cerebrovascular accident, myocardial infarction, medications (corticosteroids, thiazides, SGLT2 inhibitors, sympathomimetics), pancreatitis, trauma 6, 3

Resolution Criteria

HHS is Resolved When:

• 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

Critical Pitfalls to Avoid

Do Not:

• Add dextrose too early (delays correction of hyperosmolarity and prolongs altered mental status) 3
• Correct osmolality faster than 3-8 mOsm/kg/h (risk of cerebral edema with 70% mortality) 3
• Start insulin before excluding hypokalemia 3
• Use bicarbonate (not recommended in HHS, no proven benefit) 3, 4, 2
• Use sliding scale insulin alone in critically ill patients 3

Common Complications:

• Cerebral edema (from overly rapid osmolality correction) 3
• Central pontine myelinolysis (from rapid osmolality changes) 2, 5
• Hypokalemia (from insulin administration) 3
• Hypoglycemia (from overzealous insulin treatment) 4
• Hyperchloremic metabolic acidosis (from excessive saline, typically transient) 3
• Fluid overload (especially in elderly and those with cardiac/renal disease) 1

Care Setting

• Admit to intensive care unit due to greater volume depletion, acute illness, and mortality up to 15% 1, 3, 7, 8
• Involve diabetes specialist team as soon as possible 1, 2
• Nurse in areas where staff experienced in HHS management 2