What is the treatment for hyperglycemia with a blood glucose level greater than 400?

Treatment of Blood Glucose Greater Than 400 mg/dL

Initiate insulin therapy immediately when blood glucose exceeds 400 mg/dL, using intravenous insulin infusion for critically ill patients or subcutaneous basal-bolus insulin for stable patients, targeting a glucose range of 140-180 mg/dL to reduce mortality while avoiding hypoglycemia. 1

Immediate Assessment

Before starting insulin, you must exclude several critical conditions:

• Check serum potassium immediately - do not start insulin if K+ <3.3 mEq/L as insulin drives potassium intracellularly and can precipitate life-threatening hypokalemia 2
• Calculate effective osmolality using 2[Na+ (mEq/L)] + glucose (mg/dL)/18 to identify hyperosmolar hyperglycemic state (HHS) if >320 mOsm/kg 2
• Obtain arterial blood gas, complete metabolic panel, and check for ketones (urine or blood) to differentiate diabetic ketoacidosis from non-ketotic hyperglycemia 2, 3
• Assess for precipitating factors including infection, myocardial infarction, stroke, or medication non-compliance 2, 4
• Evaluate neurological status carefully as altered mental status may represent hyperglycemic encephalopathy or concurrent stroke 2

Insulin Therapy Protocol

For Critically Ill Patients

Use continuous intravenous regular insulin infusion starting at 0.1 units/kg/hour after confirming adequate potassium levels 1, 2, 3:

• Dilute insulin to 1 IU/mL concentration for IV administration 3
• Target glucose of 140-180 mg/dL, not normoglycemia - the NICE-SUGAR trial demonstrated that intensive targets (80-110 mg/dL) increased mortality by 27.5% vs 25% compared to moderate targets 1
• Monitor blood glucose hourly until stable, then every 2 hours 3
• Add glucose infusion (100-150 g/day) once blood glucose falls below 252 mg/dL (14 mmol/L) to prevent hypoglycemia 3
• Use validated written or computerized protocols that allow predefined adjustments in infusion rate 1, 4

For Non-Critically Ill Stable Patients

Initiate subcutaneous basal-bolus insulin regimen 1, 4:

• Basal insulin: Start at 0.1-0.2 units/kg body weight or 10 units (glargine, detemir, or degludec) 1
• Prandial insulin: Add rapid-acting insulin (lispro, aspart, or glulisine) before each meal 1
• Correction insulin: Include supplemental doses for glucose elevations 1
• Strongly avoid sliding-scale insulin alone - this approach is ineffective and associated with poor outcomes 1, 4, 3

Special Consideration for Glucose >300 mg/dL

For pre-prandial glucose ≥300 mg/dL without ketosis, give 6 units ultra-rapid analogue insulin subcutaneously and recheck glucose 3 hours later 4. If ketones are present with glucose ≥300 mg/dL and ketonemia ≥1.5 mmol/L, consider ICU transfer for IV insulin therapy 4.

Target Glucose Ranges

The American Diabetes Association recommends 140-180 mg/dL for most hospitalized patients 1, 4, 3. This moderate target reduces mortality compared to intensive control while minimizing hypoglycemia risk, which increases 10- to 15-fold with tighter targets 1.

More stringent targets of 110-140 mg/dL may be appropriate only for highly selected patients (such as cardiac surgery patients) if achievable without significant hypoglycemia 1, 4.

Transitioning from IV to Subcutaneous Insulin

When the patient stabilizes and glucose is <300 mg/dL 2:

• Start subcutaneous basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 2, 4
• Calculate subcutaneous dose as 60-80% of total 24-hour IV insulin requirement 4
• Divide the dose: give half as basal insulin and divide the other half by 3 for prandial doses 4

Critical Pitfalls to Avoid

Hypoglycemia carries substantial mortality risk, particularly in elderly patients (≥70 years have twofold increased mortality) 2. The intensive glycemic control approach increases hypoglycemia rates dramatically without improving outcomes 1.

Avoid rapid correction of severe hyperglycemia as this can precipitate cerebral edema, especially concerning in patients with neurological symptoms 2. Target glucose of 180-270 mg/dL within 24 hours, not immediate normalization 2.

Never use sliding-scale insulin as sole therapy - this is strongly discouraged by all major guidelines and associated with poor glycemic control 1, 4, 3.

Ensure adequate potassium replacement before and during insulin therapy as hypokalemia can be life-threatening 2, 5, 6.

Renal and Cardiac Considerations

Avoid metformin and SGLT2 inhibitors in the acute setting given risk of acute kidney injury from severe dehydration 2. Adjust insulin dosing for renal impairment as decreased clearance increases hypoglycemia risk 2.

Monitor for fluid retention if using thiazolidinediones, as these can precipitate heart failure when combined with insulin 5.

Monitoring Requirements

• Blood glucose every 4-6 hours minimum for non-eating patients 1
• Pre-meal glucose checks for patients who are eating 1
• Every 30 minutes to 2 hours during IV insulin infusion 1
• Reassess insulin regimen if glucose falls below 100 mg/dL 4
• Modify regimen when glucose <70 mg/dL unless easily explained by missed meals 4

Discharge Planning

Schedule follow-up within 1-2 weeks with endocrinology or primary care 2, 3. Educate patients that persistent glucose >300 mg/dL requires immediate medical attention 2. Provide sick-day management education to prevent recurrent hyperglycemic crisis 2.