What should be done for a patient with severe hyperglycemia not responding to a regular insulin infusion at 10ml/hr?

Management of Refractory Hyperglycemia on Insulin Infusion

When severe hyperglycemia persists despite regular insulin infusion at 10ml/hr, you must first verify the infusion is actually delivering insulin properly, then systematically investigate and address underlying causes of insulin resistance while escalating the insulin infusion rate up to 10 U/kg/hr if needed. 1

Immediate Assessment and Troubleshooting

Verify Insulin Delivery

• Check that the IV line is patent and the infusion pump is functioning correctly - mechanical failure is a common but overlooked cause of apparent insulin resistance 2
• Confirm the insulin concentration in the syringe is correct (typically 1 U/mL for regular insulin) 3
• Ensure the IV catheter has not infiltrated or become occluded 2

Assess for Life-Threatening Complications

• Immediately check for diabetic ketoacidosis (DKA) if blood glucose >16.5 mmol/L (300 mg/dL) by measuring serum or urine ketones 3
• If ketonuria ≥2+ or ketonaemia ≥1.5 mmol/L, this indicates DKA requiring ICU transfer and continuation of IV insulin with aggressive fluid resuscitation 3, 1
• In type 2 diabetes patients, measure serum osmolality to exclude hyperosmolar hyperglycemic state (HHS) - osmolality >320 mOsm/kg requires ICU management 3

Escalation of Insulin Therapy

Increase Infusion Rate Systematically

• If plasma glucose does not fall by 50 mg/dL (2.8 mmol/L) in the first hour after verifying adequate hydration, double the insulin infusion rate every hour until achieving a steady glucose decline of 50-75 mg/dL/hr 3
• The initial standard rate of 0.1 U/kg/hr (approximately 5-7 U/hr in adults) can be escalated significantly 3
• In refractory cases with documented myocardial dysfunction or shock, insulin infusion rates up to 10 U/kg/hr may be required 3, 1

Target Glucose Reduction

• Aim for glucose reduction of 50-75 mg/dL per hour - faster correction risks neurological complications 3, 1
• Once glucose reaches 250 mg/dL in DKA or 300 mg/dL in HHS, decrease infusion to 0.05-0.1 U/kg/hr and add dextrose to IV fluids 3

Address Underlying Causes of Insulin Resistance

Major Insulin Resistance Indicators

• If the insulin requirement exceeds 5 IU/hr, this indicates major insulin resistance requiring investigation of precipitating factors 3

Common Causes to Investigate and Treat

• Infection or sepsis - the most common cause of insulin resistance in hospitalized patients 3
• Inadequate hydration - dehydration significantly impairs insulin action and must be corrected with IV fluids 3
• Medications causing hyperglycemia: corticosteroids, vasopressors (especially high-dose), thyroid replacement therapy, oral contraceptives 4
• Endocrine disorders: hyperthyroidism, Cushing's syndrome, acromegaly, pheochromocytoma 4
• Acute stress states: myocardial infarction, stroke, trauma, surgery 3

Monitoring Requirements

Glucose Monitoring Frequency

• Measure blood glucose every 1-2 hours during periods of glycemic instability on IV insulin infusion 3, 1
• Continue frequent monitoring until glucose stabilizes within target range of 7.8-11.1 mmol/L (140-200 mg/dL) 3, 1

Additional Monitoring

• Check serum potassium every 2-4 hours initially as insulin therapy drives potassium intracellularly, risking life-threatening hypokalemia 3
• Add potassium to IV fluids once serum K+ <5.3 mEq/L and urine output is adequate 3
• Monitor for hypoglycemia vigilantly - severe hypoglycemia risk increases with aggressive insulin therapy 3

Critical Pitfalls to Avoid

• Never assume the insulin infusion is working without verifying mechanical delivery - pump malfunction or line problems are frequently missed 2
• Do not continue the same insulin rate if glucose fails to decline by 50 mg/dL in the first hour - this represents treatment failure requiring escalation 3
• Avoid correcting glucose faster than 75 mg/dL per hour to prevent cerebral edema and other neurological complications 3, 1
• Never stop insulin infusion in type 1 diabetes patients even if glucose normalizes, as this will precipitate ketoacidosis - instead add dextrose 3, 1
• Do not overlook hypokalemia - insulin therapy without potassium replacement can cause fatal cardiac arrhythmias 3

When Conservative Measures Fail

If hyperglycemia remains refractory despite:

• Verified insulin delivery at escalating doses
• Adequate hydration
• Treatment of underlying causes

Consider adding ultra-rapid acting insulin analogues subcutaneously (6 IU) in addition to the IV infusion for patients not in DKA/HHS 3. However, if ketosis is present or the patient shows signs of hemodynamic instability, transfer to ICU is mandatory for intensive monitoring and potential need for rates up to 10 U/kg/hr 3, 1.