How should I manage an inpatient with a serum glucose of 600 mg/dL?

Management of Inpatient Glucose 600 mg/dL

Immediately evaluate for hyperosmolar hyperglycemic state (HHS) and initiate aggressive intravenous fluid resuscitation as the first-line intervention, followed by insulin therapy only after partial fluid repletion.

Immediate Diagnostic Assessment

• Check effective serum osmolality using the formula: 2[measured Na (mEq/L)] + glucose (mg/dL)/18, with HHS diagnosed at ≥320 mOsm/kg H₂O 1.
• Obtain arterial blood gas, serum electrolytes with anion gap, BUN, creatinine, serum ketones (preferably β-hydroxybutyrate), complete blood count, urinalysis with ketones, ECG, and HbA1c immediately upon suspicion of HHS 1.
• Measure corrected serum sodium by adding 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation above 100 mg/dL 1.
• Check for ketones (urine or blood) to distinguish HHS from diabetic ketoacidosis (DKA) or mixed presentations; HHS shows small or absent ketones (ketonemia ≤3.0 mmol/L) 1.
• Assess mental status carefully, as altered consciousness correlates with hyperosmolarity severity and is more frequent in HHS than DKA, though preserved alertness does not exclude HHS when metabolic criteria are met 1.
• Obtain bacterial cultures (blood, urine, throat) if infection is suspected, and chest X-ray if pneumonia is suspected, as infection is the most common precipitating factor 1.

Fluid Resuscitation Protocol (First Priority)

• Begin with 0.9% saline at 15–20 mL/kg/hour (approximately 1–1.5 L/hour in adults) for the first 1–2 hours to restore circulating volume and ensure vital organ perfusion 1, 2.
• Total body water deficit in HHS averages 9 liters (100–220 mL/kg), and aim to correct estimated fluid deficits within 24 hours 1.
• Limit osmolality reduction to 3–8 mOsm/kg/hour to minimize risk of cerebral edema and central pontine myelinolysis 1, 2.
• Once initial volume is restored, switch to 0.45% saline if corrected sodium is normal or elevated, continuing at 250–500 mL/hour depending on hydration status and corrected sodium 1.
• Monitor urine output to ensure adequate renal perfusion (target ≥0.5 mL/kg/hour) before initiating potassium replacement 1.

Insulin Therapy (Second Priority)

• Withhold insulin until blood glucose is no longer falling with IV fluids alone, unless ketonemia is present 1.
• Once glucose stops declining with fluids (or if ketonemia is present), initiate with IV bolus of regular insulin at 0.15 units/kg body weight, followed by continuous infusion at 0.1 unit/kg/hour (5–7 units/hour in adults) 1.
• Target glucose reduction of 50–75 mg/dL/hour; if plasma glucose does not fall by 50 mg/dL from initial value in the first hour, check hydration status and if acceptable, double insulin infusion every hour until steady glucose decline of 50–75 mg/hour is achieved 1.
• When plasma glucose reaches 250–300 mg/dL, add 5% or 10% dextrose to IV fluids containing 0.45% saline, and reduce insulin infusion to 0.05–0.1 units/kg/hour 1.
• Maintain glucose between 250–300 mg/dL until hyperosmolarity and mental status improve, rather than aggressively lowering to normal ranges 1.

Potassium Management

• If serum potassium <3.3 mEq/L, hold insulin and give potassium replacement until potassium ≥3.3 mEq/L to prevent life-threatening hypokalemia 1.
• Once renal function is assured and serum potassium is known, add potassium to IV fluids at 20–30 mEq/L (2/3 KCl and 1/3 KPO₄) 1.
• Total body potassium deficit in HHS is 5–15 mEq/kg and requires close monitoring, as insulin administration drives potassium intracellularly 1.
• Monitor serum potassium every 2–4 hours during initial management 1.

Critical Monitoring Parameters

• Draw blood every 2–4 hours to determine serum electrolytes, glucose, urea, creatinine, osmolality, and venous pH 1.
• Calculate effective osmolality at each interval using the formula above 1.
• Monitor for signs of fluid overload, particularly in elderly patients or those with widened alveolo-arteriolar oxygen gradient or pulmonary rales on initial examination 1.
• Assess mental status frequently, as improvement correlates with successful osmolality correction 1.

Resolution Criteria

• HHS is considered resolved when: osmolality <300 mOsm/kg, hypovolemia is corrected (urine output ≥0.5 mL/kg/hour), cognitive status returns to pre-morbid state, and blood glucose <15 mmol/L (270 mg/dL) 1, 2.

Common Pitfalls to Avoid

• Do not add dextrose too early, as this can delay correction of hyperosmolarity and prolong altered mental status 1.
• Avoid overzealous fluid administration that could precipitate noncardiogenic pulmonary edema 1.
• Do not use bicarbonate in HHS, as pH is typically ≥7.30 and no prospective studies support its use 1.
• Never completely discontinue insulin once started, even if glucose normalizes; continue at reduced rate with dextrose-containing fluids 1.
• Avoid overzealous phosphate therapy, which can cause severe hypocalcemia 1.

Precipitating Factor Management

• Identify and treat underlying triggers: infection (most common), acute cerebrovascular accident, myocardial infarction, medications affecting carbohydrate metabolism (corticosteroids, thiazide diuretics, SGLT2 inhibitors), or non-compliance with therapy 1.
• Mortality rates approach 15% in HHS, higher than DKA, emphasizing the importance of identifying and treating precipitating causes 1, 2.

Transition to Subcutaneous Insulin

• Ensure overlap between stopping IV insulin and initiating subcutaneous insulin to prevent rebound hyperglycemia 1.
• Calculate total subcutaneous dose as approximately 60–80% of the 24-hour IV insulin requirement, split 50% basal and 50% prandial 1.
• Give first subcutaneous basal insulin dose 2–4 hours before stopping IV infusion 1.