What is the role of glucagon in treating beta blocker (beta-adrenergic blocking agent) overdoses?

Glucagon's Role in Beta Blocker Overdose Management

Glucagon is a reasonable treatment for beta blocker overdose-induced bradycardia and hemodynamic compromise, working by activating hepatic adenyl cyclase to bypass blocked beta receptors and increase heart rate and cardiac contractility. 1

Mechanism of Action

Glucagon counteracts beta blocker toxicity through a mechanism that bypasses the blocked beta-adrenergic receptors:

• Acts as a vasoactive polypeptide that activates hepatic adenyl cyclase to promote glycogenolysis 1
• Increases heart rate, myocardial contractility, and improves atrioventricular conduction 2
• Produces hemodynamic effects regardless of beta-adrenoceptor blockade, as demonstrated in randomized clinical trials 3
• Works through a separate G-protein coupled receptor pathway that is not affected by beta blockade

Dosing Protocol

According to the 2018 ACC/AHA/HRS guidelines and AHA special situations guidelines, the recommended dosing for beta blocker overdose is:

1. Initial bolus: 3-10 mg administered slowly over 3-5 minutes 1
2. Maintenance infusion: 3-5 mg/hour 1
   • Effects are transient, making continuous infusion necessary
   • Infusion should be titrated to achieve adequate hemodynamic response

For cardiac arrest situations specifically:

• Standard therapy is a bolus of 3-10 mg given over 3-5 minutes 1
• Followed by infusion of 3-5 mg/hour 1

Clinical Evidence

The evidence supporting glucagon use in beta blocker overdose is primarily from case reports, case series, and animal studies:

• The largest human case series included only 9 patients 1
• A 2020 randomized crossover study demonstrated that high-dose glucagon had significant hemodynamic effects regardless of beta-blockade 3
• A systematic review found that in animal models, glucagon consistently increased heart rate at least transiently but had variable effects on blood pressure 4

Important Considerations and Pitfalls

1. Side effects:

   • Nausea and vomiting (80% of patients) 3
   • Particular concern when airway protection is compromised 1
   • Consider antiemetic pretreatment

2. Supply planning:

   • Treatment may require >100 mg in a 24-hour period 1
   • Early planning for adequate glucagon supply is essential

3. Administration method:

   • Continuous infusion may be preferable to bolus injections for sustained effect 3

4. Alternative/adjunctive therapies:

   • High-dose insulin therapy (1 unit/kg bolus followed by 0.5-1 units/kg/hour) 1, 5
   • Intravenous calcium for calcium channel blocker overdose 1
   • Adrenergic pressor support may be needed for shock 1

Treatment Algorithm for Beta Blocker Overdose

1. Initial assessment: Evaluate for bradycardia, hypotension, and signs of hemodynamic compromise
2. First-line therapy: High-dose glucagon for symptomatic bradycardia and hypotension 6
   • Administer bolus of 3-10 mg over 3-5 minutes
   • Follow with infusion of 3-5 mg/hour, titrated to response
3. Monitor for response: Heart rate, blood pressure, cardiac output
4. Add second-line therapy if inadequate response:
   • High-dose insulin therapy (Class IIa recommendation) 1
   • Vasopressors as needed for shock
5. Supportive care: Airway protection, especially if vomiting occurs

Glucagon remains a cornerstone therapy for beta blocker overdose despite limited high-quality evidence, with both guidelines and clinical experience supporting its use as a reasonable intervention to improve outcomes in these potentially fatal poisonings.