Immediate Treatment for Hyperosmolar Hyperglycemia Syndrome
Begin aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 ml/kg/h (1-1.5 L in the first hour) as the cornerstone of immediate HHS management, and delay insulin administration until fluid replacement is underway and the glucose stops falling with fluids alone. 1, 2
Initial Assessment and Stabilization
Upon presentation, immediately obtain arterial blood gases, complete blood count, urinalysis, blood glucose, BUN, electrolytes, chemistry profile, creatinine, and ECG 3, 1. Calculate effective serum osmolality using the formula: 2[measured Na (mEq/l)] + glucose (mg/dl)/18 to confirm the diagnosis (should be >320 mOsm/kg H₂O) 1, 2.
Critical diagnostic criteria include: blood glucose >600 mg/dl, arterial pH >7.3, bicarbonate >15 mEq/l, and only mild ketonuria or ketonemia 3, 1, 4.
Fluid Resuscitation Protocol
The primary immediate intervention is aggressive volume expansion with 0.9% NaCl at 15-20 ml/kg/h during the first hour to restore intravascular volume and renal perfusion 1, 4, 2. This typically translates to 1-1.5 L in the average adult 1, 4.
After the initial hour, adjust fluid choice based on corrected serum sodium (add 1.6 mEq to sodium for each 100 mg/dl glucose >100 mg/dl) 3:
- Use 0.45% NaCl at 4-14 ml/kg/h if corrected sodium is normal or elevated 3
- Continue 0.9% NaCl at similar rates if corrected sodium is low 3
Target fluid replacement to correct estimated deficits within 24 hours (typical losses are 100-220 ml/kg) 3, 1, 2. The induced change in serum osmolality should not exceed 3-8 mOsm/kg/h to minimize risk of cerebral edema and central pontine myelinolysis 3, 5, 2.
Insulin Administration Timing
A critical distinction from DKA: withhold insulin initially until the blood glucose stops falling with IV fluids alone, unless significant ketonaemia is present 5, 2. This represents a key difference from older protocols, as fluid replacement alone will cause blood glucose to fall, and early insulin use before adequate fluid resuscitation may be detrimental 5, 2.
When insulin is indicated:
- Start continuous IV regular insulin at 0.1 U/kg/h (typically 5-10 units/hour) 1, 4
- Never start insulin if serum potassium <3.3 mEq/L due to risk of fatal cardiac arrhythmias 4
- When glucose reaches 300 mg/dl, decrease insulin to 0.05-0.1 U/kg/h (3-6 U/h) 1
- Add 5-10% dextrose to IV fluids when glucose falls below 300 mg/dl to prevent hypoglycemia while continuing to treat hyperosmolarity 1
Potassium Replacement
Once renal function is assured (urine output established) and serum potassium is known, add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄) 3, 1, 4. This is essential regardless of initial potassium level, as insulin therapy drives potassium intracellularly and total body potassium is typically severely depleted 1, 4.
Monitoring Requirements
Monitor vital signs, mental status, fluid input/output hourly 1, 4. Check blood glucose every 1-2 hours until stable 1. Monitor electrolytes (sodium, potassium, chloride, bicarbonate, phosphate, magnesium) every 2-4 hours during initial treatment 1. Calculate effective serum osmolality regularly to guide fluid management and ensure the decline is 3-8 mOsm/kg/h 1, 2.
Critical Pitfalls to Avoid
Do not use hypotonic fluids initially despite the hyperosmolar state—restoration of circulating volume takes priority, and an initial rise in sodium is expected and not itself an indication for hypotonic fluids 5, 2.
Do not start insulin before adequate fluid resuscitation as this differs fundamentally from DKA management and may worsen outcomes 5, 2.
Exercise extreme caution in elderly patients and those with cardiac or renal compromise—use more conservative fluid rates with closer hemodynamic monitoring to avoid iatrogenic fluid overload 3, 1, 4.
Do not use bicarbonate therapy routinely, as it has not been shown to improve outcomes in HHS 3, 4.
Special Populations
In pediatric patients (<20 years), use 0.9% NaCl at 10-20 ml/kg/h initially, not exceeding 50 ml/kg over the first 4 hours to minimize cerebral edema risk 3, 4.