What is the treatment for hyperosmolar hyperglycemic state (HHS)?

Treatment of Hyperosmolar Hyperglycemic State (HHS)

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

Initial Assessment and Monitoring

Upon presentation, immediately obtain arterial blood gases, complete blood count with differential, urinalysis, plasma glucose, blood urea nitrogen, electrolytes, chemistry profile, creatinine levels, and electrocardiogram. 3, 1 Calculate effective serum osmolality using the formula: 2[measured Na (mEq/L)] + glucose (mg/dL)/18, with HHS diagnosed at ≥320 mOsm/kg H₂O. 1, 4

Correct serum sodium for hyperglycemia by adding 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation above 100 mg/dL. 3, 4 This corrected sodium value guides subsequent fluid selection.

Obtain chest X-ray and cultures as clinically indicated to identify precipitating infections, which are the most common trigger of HHS. 1, 5

Fluid Resuscitation Strategy

The cornerstone of HHS treatment is aggressive fluid replacement, as total body water deficit approximates 9 liters (100-220 mL/kg). 1, 6

First Hour (0-60 minutes)

• Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/h (1-1.5 L in average adult) to restore circulatory volume and renal perfusion. 1, 6

Subsequent Fluid Management (1-24 hours)

• If corrected serum sodium is normal or elevated: switch to 0.45% NaCl at 4-14 mL/kg/h. 3
• If corrected serum sodium is low: continue 0.9% NaCl at similar rate. 3
• Aim to correct estimated fluid deficits within 24 hours, with osmolality reduction not exceeding 3-8 mOsm/kg/h to prevent central pontine myelinolysis. 1, 2, 6

Critical pitfall: Rapid osmolality correction can precipitate devastating neurological complications including central pontine myelinolysis and cerebral edema. 2, 7 Monitor calculated osmolality every 2-4 hours, not just individual components. 1, 4

In patients with renal or cardiac compromise, perform frequent assessment of cardiac, renal, and mental status during fluid resuscitation to avoid iatrogenic fluid overload. 3

Insulin Therapy

The timing of insulin initiation in HHS differs fundamentally from DKA management. 2, 7

When to Start Insulin

• Withhold insulin until blood glucose level stops falling with IV fluids alone, unless ketonemia is present. 2, 6 Fluid replacement alone will cause a fall in blood glucose, and early insulin use before adequate fluid resuscitation may be detrimental. 2

Insulin Dosing Protocol

Once glucose stabilizes with fluids or ketonemia is present:

• Adults: 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). 3, 1
• Pediatric patients (<20 years): No initial bolus; start continuous infusion at 0.1 unit/kg/h. 3

Target Glucose Decline

• Plasma glucose should decrease at 50-75 mg/dL/h. 3, 1
• If glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration, then double insulin infusion hourly until steady decline achieved. 3

Glucose Management During Treatment

• When plasma glucose reaches 300 mg/dL in HHS (250 mg/dL in pediatrics), decrease insulin infusion to 0.05-0.1 units/kg/h (3-6 units/h) and add 5% dextrose to IV fluids. 3, 1
• Target blood glucose of 10-15 mmol/L (180-270 mg/dL) in the first 24 hours. 6

Electrolyte Management

Potassium Replacement

Total body potassium deficit in HHS is 5-15 mEq/kg and requires meticulous monitoring. 1, 4

• If serum potassium <3.3 mEq/L: Hold insulin and give potassium replacement until potassium ≥3.3 mEq/L to prevent life-threatening hypokalemia. 3, 4
• Once renal function assured and potassium known: Add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄). 3, 1

Sodium Management

An initial rise in sodium level during treatment is expected and physiologic—this is NOT an indication for hypotonic fluids. 2 The corrected sodium should guide fluid selection, not the measured sodium.

Bicarbonate

Bicarbonate administration is generally not recommended in HHS. 1 HHS typically presents with pH >7.3 and bicarbonate >15 mEq/L, distinguishing it from DKA. 1, 4

Monitoring During Treatment

• Blood glucose: Check every 1-2 hours until stable. 1
• Serum electrolytes, BUN, creatinine, calculated osmolality: Every 2-4 hours. 1
• Fluid input/output, vital signs, mental status: Assess frequently. 1
• Serum osmolality: Monitor regularly to ensure reduction of 3-8 mOsm/kg/h. 1, 6

Transition to Subcutaneous Insulin

Administer basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia. 1 Recent evidence suggests low-dose basal insulin analog given concurrently with IV insulin may prevent rebound hyperglycemia. 1

Resolution Criteria

HHS is considered resolved when:

• Osmolality <300 mOsm/kg 6
• Hypovolemia corrected (urine output ≥0.5 mL/kg/h) 6
• Cognitive status returned to pre-morbid state 6
• Blood glucose <15 mmol/L (270 mg/dL) 6

Treatment of Precipitating Causes

Identify and treat underlying causes, especially infections, as appropriate management of precipitating illnesses reduces the high mortality associated with HHS. 1, 8 Common precipitants include infections, acute cerebrovascular accident, myocardial infarction, and medications affecting carbohydrate metabolism. 4, 5

Special Populations

Pediatric Patients (<20 years)

• Initial fluid: 0.9% NaCl at 10-20 mL/kg/h for first hour, not exceeding 50 mL/kg over first 4 hours. 3
• Critical: Correct dehydration at rate not exceeding 3 mOsm/h to avoid cerebral edema. 5, 7
• Continue fluid therapy to replace deficit evenly over 48 hours using 0.45-0.9% NaCl at 1.5 times maintenance requirements. 3
• No initial insulin bolus; start continuous infusion only. 3
• Monitor mental status closely to identify iatrogenic complications. 3

Elderly and Patients with Comorbidities

Exercise particular caution with fluid administration in elderly patients and those with renal or cardiac compromise, as they are at higher risk for fluid overload. 3, 6

Level of Care

Patients with suspected HHS should be immediately evaluated and treated in the inpatient setting, preferably in an intensive care unit, due to greater volume depletion and typical triggering by acute illness. 4 The diabetes specialist team should be involved as soon as possible, and patients should be nursed in areas where staff are experienced in HHS management. 2