What are the recommended doses for high‑dose insulin euglycemic therapy (initial IV bolus and continuous infusion), dextrose infusion, norepinephrine, epinephrine, and glucagon in the treatment of severe beta‑blocker overdose?

Recommended Doses for Severe Beta-Blocker Overdose

For severe beta-blocker overdose, initiate high-dose insulin with a 1 unit/kg IV bolus followed by continuous infusion at 1-10 units/kg/hour, titrated to hemodynamic response; administer dextrose 0.5 g/kg/hour (typically 10-25 grams IV bolus initially) to maintain euglycemia; use glucagon 50 mcg/kg (3-5 mg) IV bolus followed by 1-15 mg/hour continuous infusion; and administer standard-dose vasopressors (norepinephrine or epinephrine) as first-line therapy for immediate blood pressure support. 1, 2

High-Dose Insulin Euglycemic Therapy (HIET)

The 2023 AHA guidelines give high-dose insulin a Class 1 recommendation (strongest level) for beta-blocker-induced hypotension refractory to or in conjunction with vasopressors 1. This represents the highest quality evidence available.

Insulin Dosing Protocol

• Initial IV bolus: 1 unit/kg 2, 3
• Continuous infusion: Start at 1 unit/kg/hour, titrate upward by 1-2 units/kg/hour every 10-15 minutes 2
• Maximum dose: Up to 10 units/kg/hour (some case reports describe 22 units/kg/hour in refractory cases) 2, 3
• Onset of action: 15-60 minutes, making it slower than catecholamines 4

Critical caveat: High-dose insulin is an inodilator that improves cardiac contractility but causes vasodilation. It should be used concurrently with norepinephrine to counteract insulin-induced vasodilation, particularly in cardiogenic shock 4. It has no role in isolated vasoplegic shock where it may worsen hypotension.

Dextrose Supplementation

• Initial bolus: 10-25 grams IV (20-50 mL of 50% dextrose or 100-250 mL of 10% dextrose) 5
• Continuous infusion: 0.5 g/kg/hour (typically 5-10% dextrose solution) 2, 6
• Monitoring: Check glucose every 15-30 minutes initially, then hourly once stable
• Target: Maintain blood glucose 100-200 mg/dL

Important: Glucose supplementation must continue throughout insulin therapy and for up to 24 hours after discontinuation due to persistent hypoglycemia risk 2.

Glucagon

The AHA gives glucagon a Class 2a recommendation (reasonable to use) for bradycardia or hypotension 1.

• Initial IV bolus: 50 mcg/kg (typically 3-5 mg for adults, 0.5-1 mg for children) 7
• Continuous infusion: 1-15 mg/hour, titrated to patient response 7
• Pediatric dosing: For children <20 kg, use 0.5 mg (0.5 mL) or 20-30 mcg/kg 8

Limitations: Glucagon often fails in severe poisoning and has significant side effects (nausea, vomiting, hypokalemia, hyperglycemia) 7. Its effectiveness is inconsistent, making it less reliable than high-dose insulin.

Vasopressors

The AHA gives vasopressors a Class 1 recommendation as initial therapy 1.

Norepinephrine (Preferred)

• Dosing: Start at 0.05-0.1 mcg/kg/min, titrate to effect (typical range 0.1-3 mcg/kg/min)
• Rationale: Should be used as first-line for immediate blood pressure support while preparing high-dose insulin 1

Epinephrine

• Dosing: 0.05-0.5 mcg/kg/min IV infusion
• Critical warning: Animal studies show epinephrine combined with vasopressin is INFERIOR to high-dose insulin, with 100% mortality in the vasopressor-only group versus 100% survival with insulin 9. High-dose vasopressors increase SVR but depress cardiac output, contributing to death 9.

Key principle: Vasopressors provide rapid initial stabilization but should be combined with or transitioned to high-dose insulin for definitive management. Increasing SVR alone in beta-blocker toxicity is detrimental 9.

Monitoring Requirements

Glucose Monitoring

• Every 15-30 minutes during insulin titration
• Hourly once stable
• Continue for 24 hours after insulin discontinuation

Electrolyte Monitoring

• Potassium: Check every 1-2 hours initially
• Mechanism: Insulin shifts potassium intracellularly (not true depletion) 2
• Replacement: Administer potassium chloride as needed to maintain K+ >3.5 mEq/L

Hemodynamic Monitoring

• Continuous cardiac monitoring
• Arterial line for beat-to-beat blood pressure
• Consider central venous access for high-dose insulin infusion

Treatment Algorithm

1. Immediate (0-5 minutes):

   • Start norepinephrine for hypotension (provides rapid effect)
   • Administer 10-25 grams dextrose IV bolus
   • Check baseline glucose and potassium

2. Early (5-15 minutes):

   • Initiate high-dose insulin: 1 unit/kg IV bolus
   • Start insulin infusion at 1 unit/kg/hour
   • Start dextrose infusion at 0.5 g/kg/hour
   • Consider glucagon 3-5 mg IV bolus if available

3. Ongoing (15-60 minutes):

   • Titrate insulin upward by 1-2 units/kg/hour every 10-15 minutes to maximum 10 units/kg/hour
   • Adjust dextrose infusion to maintain euglycemia
   • Begin weaning vasopressors as hemodynamics improve (typically 6-8 hours after maximum insulin dose) 3

4. Refractory cases:

   • Consider VA-ECMO (Class 2a recommendation) for cardiogenic shock unresponsive to maximal pharmacotherapy 1

Common Pitfalls

• Waiting too long to start high-dose insulin: It should be initiated early, not after conventional therapy fails 3, 10
• Inadequate glucose supplementation: Hypoglycemia is the most common adverse effect and can persist long after insulin cessation 2, 4
• Using vasopressors alone: This increases SVR but worsens cardiac output and survival 9
• Stopping potassium monitoring: Hypokalemia can develop rapidly and persist 4
• Premature insulin discontinuation: Continue for at least 24 hours after hemodynamic stability due to prolonged beta-blocker effects