What is the treatment for beta blocker toxicity using glucagon?

Glucagon for Beta Blocker Toxicity

For beta blocker toxicity, glucagon should be administered as a bolus of 3-10 mg IV over 3-5 minutes, followed by an infusion of 3-5 mg/hour, titrated to achieve adequate hemodynamic response. 1

Mechanism of Action

Glucagon works by bypassing the blocked beta receptors and activating adenyl cyclase directly, which increases intracellular cAMP levels and promotes positive inotropic and chronotropic effects. This makes it particularly valuable in beta blocker toxicity where the normal beta-adrenergic pathways are blocked.

Treatment Algorithm for Beta Blocker Toxicity

1. Initial Assessment

   • Identify signs of beta blocker toxicity: bradycardia, hypotension, heart block, decreased cardiac contractility
   • Some beta blockers (e.g., propranolol, sotalol) may also prolong QRS and QT intervals 1

2. First-Line Treatments

   • Vasopressors: Begin with epinephrine or norepinephrine (more effective than dopamine) for immediate blood pressure support 1, 2
   • High-Dose Insulin Therapy: 1 U/kg IV bolus followed by infusion of 0.5-1 U/kg/hour with dextrose supplementation 1, 2, 3
     • Monitor glucose every 15-30 minutes initially
     • Target glucose 100-250 mg/dL
     • Expect moderate hypokalemia (target 2.5-2.8 mEq/L) 1

3. Glucagon Administration (Class IIa, LOE C-LD) 1

   • Bolus dose: 3-10 mg IV administered slowly over 3-5 minutes
   • Infusion: 3-5 mg/hour (0.05-0.10 mg/kg/hour)
   • Titration: Adjust based on heart rate, blood pressure, and perfusion
   • Supply planning: Ensure adequate supply (may require >100 mg/24 hours) 1
   • Airway protection: Secure airway before administration as glucagon commonly causes vomiting 1, 2

4. Additional Therapies for Refractory Cases

   • Calcium (Class IIb, LOE C): 0.3 mEq/kg IV calcium (0.6 mL/kg of 10% calcium gluconate or 0.2 mL/kg of 10% calcium chloride) over 5-10 minutes 1
     • For central line administration, prefer calcium chloride
     • For peripheral line, use calcium gluconate to avoid tissue injury
   • Consider VA-ECMO for cases unresponsive to pharmacological interventions 2, 4

Monitoring During Treatment

• Continuous cardiac monitoring (ECG, heart rate, blood pressure)
• Frequent assessment of mental status and peripheral perfusion
• Regular monitoring of serum glucose, potassium, and calcium levels
• Monitor for signs of improvement: increased heart rate, improved blood pressure, better tissue perfusion

Important Considerations and Pitfalls

• Avoid Class IA (quinidine, procainamide), Class IC (flecainide, propafenone), or Class III (amiodarone, sotalol) antiarrhythmics as they may worsen cardiac toxicity 1, 2
• Animal studies suggest that concomitant use of dopamine alone or with isoproterenol and milrinone may decrease glucagon effectiveness 1
• While glucagon has shown consistent effects on increasing heart rate, its effects on blood pressure are less reliable 5, 4
• High-dose insulin therapy has emerged as a superior treatment in terms of survival outcomes in both animal models and human case reports 4, 3
• The evidence supporting glucagon use is primarily from animal studies and case reports/series, with no randomized controlled trials in humans 5, 6

Glucagon remains a reasonable second-line therapy for beta blocker toxicity, particularly when high-dose insulin therapy is insufficient or unavailable, but should be used as part of a comprehensive approach that includes vasopressors and potentially calcium administration for severe cases.