How to manage hyperglycemia above 400 mg/dL?

Management of Blood Glucose Above 400 mg/dL

For blood glucose levels above 400 mg/dL, immediately assess for diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) through laboratory evaluation including electrolytes, anion gap, and ketones, then initiate intravenous insulin infusion at 0.1 units/kg/hour along with aggressive fluid resuscitation with normal saline. 1, 2

Immediate Assessment

When encountering glucose levels >400 mg/dL, you must first determine if this represents a hyperglycemic crisis:

• Check arterial blood gases, complete blood count, urinalysis, plasma glucose, electrolytes, BUN, creatinine, and obtain an ECG immediately 1
• DKA criteria: pH <7.3, bicarbonate <15 mEq/L, moderate ketonuria/ketonemia 1
• HHS criteria: pH >7.3, bicarbonate >15 mEq/L, effective serum osmolality >320 mOsm/kg 1
• Calculate corrected sodium: add 1.6 mEq to measured sodium for each 100 mg/dL glucose above 100 mg/dL 1

Fluid Resuscitation Protocol

Begin aggressive fluid replacement immediately, as dehydration is a critical component of severe hyperglycemia:

• Start with 0.9% normal saline at 10-20 ml/kg/hour (approximately 1-1.5 liters in the first hour for adults) 1
• In severely dehydrated patients, repeat this bolus, but do not exceed 50 ml/kg over the first 4 hours 1
• Continue fluid therapy at 1.5 times the 24-hour maintenance requirements (approximately 5 ml/kg/hour) to replace deficit evenly over 48 hours 1
• Switch to 0.45-0.9% NaCl based on corrected serum sodium levels, ensuring osmolality decrease does not exceed 3 mOsm/kg/H2O per hour 1

Insulin Therapy

For adults with severe hyperglycemia (>400 mg/dL), use continuous intravenous insulin infusion:

• Give an initial IV bolus of regular insulin at 0.15 units/kg body weight 1
• Follow immediately with continuous infusion of regular insulin at 0.1 units/kg/hour (typically 5-7 units/hour in adults) 1
• Target a glucose decline of 50-75 mg/dL per hour 1
• If glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration, then double the insulin infusion rate hourly until achieving steady decline 1

Critical timing consideration: Once glucose reaches 250 mg/dL, change IV fluids to 5% dextrose with 0.45-0.75% NaCl to prevent hypoglycemia while continuing insulin to clear ketones 1

Potassium Management

Hypokalemia occurs in approximately 50% of patients during treatment and severe hypokalemia (<2.5 mEq/L) increases mortality: 1

• Once renal function is confirmed and serum potassium is known, add 20-40 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO4) 1
• Do not start insulin if potassium is <3.3 mEq/L until potassium is repleted 1
• Monitor potassium levels closely throughout treatment 1

Setting-Specific Considerations

For critically ill patients (ICU setting):

• Maintain glucose between 140-180 mg/dL once IV insulin is initiated 1
• Use validated computerized or written protocols for insulin infusion adjustments 2
• Avoid glucose targets <110 mg/dL due to increased hypoglycemia risk 1

For non-critically ill patients with glucose >400 mg/dL:

• If patient can tolerate oral intake and is hemodynamically stable, consider subcutaneous insulin with rapid-acting analogue 6 units for pre-prandial glucose ≥300 mg/dL without ketosis, rechecking in 3 hours 2
• However, if ketones are present (ketonemia ≥1.5 mmol/L), transfer to ICU for IV insulin therapy 2

Transition to Subcutaneous Insulin

When discontinuing IV insulin after glucose stabilization:

• Start subcutaneous basal insulin 1-2 hours before stopping IV infusion 2
• Calculate basal insulin dose as 60-80% of total daily IV insulin dose 2
• Use half of the 24-hour IV insulin total as long-acting basal insulin, and divide the other half by 3 for rapid-acting insulin doses before meals 2

Common Pitfalls to Avoid

• Never use sliding-scale insulin alone - it is strongly discouraged and associated with poor outcomes 1, 2, 3
• Avoid overly aggressive glucose lowering - targets <110 mg/dL increase hypoglycemia risk and mortality 1
• Do not stop IV insulin abruptly - ensure 1-2 hour overlap with subcutaneous insulin to prevent rebound hyperglycemia 2
• Monitor mental status closely - rapid changes may indicate cerebral edema (especially in younger patients) or iatrogenic complications 1
• Reassess insulin regimen if glucose falls below 100 mg/dL and modify when <70 mg/dL unless explained by missed meals 1, 2