What is the immediate management for a patient presenting with Hyperosmolar Hyperglycemic State (HHS)?

Immediate Management of Hyperosmolar Hyperglycemic State (HHS)

Begin aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 ml/kg/h during the first hour, and delay insulin therapy until blood glucose stops falling with IV fluids alone unless ketonemia is present. 1, 2, 3

Initial Assessment and Diagnosis

Confirm HHS diagnosis immediately with the following criteria: 1, 2

• Blood glucose ≥600 mg/dL
• Effective serum osmolality ≥320 mOsm/kg H₂O (calculated as: 2[measured Na (mEq/L)] + glucose (mg/dL)/18)
• Arterial pH ≥7.30
• Serum bicarbonate ≥15 mEq/L
• Small or absent ketones (ketonemia ≤3.0 mmol/L)

Obtain these laboratory tests immediately: 1, 2

• Arterial blood gases
• Complete blood count with differential
• Comprehensive metabolic panel (electrolytes, BUN, creatinine, glucose)
• Serum ketones (β-hydroxybutyrate preferred over nitroprusside method)
• Urinalysis with urine ketones
• Electrocardiogram
• HbA1c
• Blood, urine, and throat cultures if infection suspected
• Chest X-ray if pneumonia suspected

Identify precipitating factors: infection (most common), myocardial infarction, stroke, medications (diuretics, corticosteroids, SGLT2 inhibitors), or non-compliance. 1, 2

Fluid Resuscitation (Priority #1)

Phase 1 (0-60 minutes): 1, 3

• Administer 0.9% NaCl at 15-20 ml/kg/h (approximately 1-1.5 L in average adult) to restore intravascular volume and renal perfusion
• This aggressive initial resuscitation is critical as total body water deficit averages 9 liters (100-220 ml/kg)

Phase 2 (1-24 hours): 1, 2, 3

• Continue fluid replacement to correct estimated deficits within 24 hours
• Adjust fluid choice based on corrected serum sodium (add 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation above 100 mg/dL)
• Target osmolality reduction of 3-8 mOsm/kg/h to prevent neurological complications including central pontine myelinolysis 1, 4, 3
• Exercise caution in elderly patients and those with cardiac/renal compromise—use slower fluid rates with closer monitoring 1

Insulin Therapy (Critical Timing)

The key distinction from DKA management: withhold insulin until blood glucose stops falling with IV fluids alone, unless ketonemia is present. 2, 4, 3 Early insulin administration before adequate fluid resuscitation may be detrimental. 4

When to start insulin: 1, 2, 3

• Once glucose plateaus despite ongoing fluid resuscitation (or immediately if ketonemia present)
• Administer IV bolus of regular insulin 0.1-0.15 units/kg body weight
• Follow with continuous IV infusion at 0.1 units/kg/h (typically 5-10 units/hour)

Insulin adjustment: 1, 2

• Target glucose decline of 50-75 mg/dL/h
• If glucose doesn't fall by 50 mg/dL in first hour, reassess hydration status; if adequate, double insulin infusion hourly until steady decline achieved
• When plasma glucose reaches 300 mg/dL, decrease insulin to 0.05-0.1 units/kg/h (3-6 units/h)
• Add 5-10% dextrose to IV fluids when glucose falls below 300 mg/dL to prevent hypoglycemia while continuing to treat hyperosmolarity
• Target glucose 250-300 mg/dL (10-15 mmol/L) in first 24 hours, not normoglycemia 1, 3

Electrolyte Replacement

Potassium management (critical to prevent cardiac complications): 1, 2

• Total body potassium deficit is 5-15 mEq/kg despite normal or elevated initial serum levels
• If serum potassium <3.3 mEq/L: hold insulin and give potassium replacement until ≥3.3 mEq/L
• Once renal function confirmed and potassium known, add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄)
• Monitor potassium every 2-4 hours initially 1

Sodium correction: 2

• An initial rise in sodium is expected as glucose falls and is NOT an indication for hypotonic fluids 4
• Calculate corrected sodium to guide management

Do NOT routinely use bicarbonate therapy—it has not been shown to improve outcomes. 1

Monitoring Requirements

Intensive monitoring is mandatory: 1, 5, 3

• Vital signs, mental status, fluid input/output: hourly
• Blood glucose: every 1-2 hours until stable
• Electrolytes (sodium, potassium, chloride, bicarbonate, phosphate, magnesium): every 2-4 hours initially
• Calculate effective serum osmolality regularly to guide therapy
• Monitor for complications: cerebral edema, myocardial infarction, stroke, vascular thrombosis

Location of care: 2, 5, 3

• Admit to intensive care unit due to high mortality (up to 15%) and need for intensive monitoring
• Involve diabetes specialist team immediately
• Ensure nursing staff experienced in HHS management

Resolution Criteria

HHS is resolved when: 3

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

Transition to Subcutaneous Insulin

When transitioning from IV to subcutaneous insulin: 1

• Administer basal insulin 2-4 hours BEFORE stopping IV insulin infusion to prevent rebound hyperglycemia
• Consider low-dose basal insulin analog in addition to IV insulin during transition

Common Pitfalls to Avoid

• Do not start insulin before adequate fluid resuscitation unless ketonemia present—this differs fundamentally from DKA management 4, 3
• Do not correct osmolality too rapidly (>8 mOsm/kg/h)—this risks central pontine myelinolysis 1, 4, 3
• Do not use hypotonic fluids initially despite elevated sodium—initial sodium rise is expected 4
• Do not target normal glucose rapidly—aim for 250-300 mg/dL in first 24 hours 1, 3
• Do not overlook precipitating factors—failure to treat underlying infection or acute illness contributes to high mortality 1, 2