Can glucagon be used to reverse beta blocker (beta-adrenergic blocking agent) overdose?

From the Guidelines

Glucagon can be used to reverse beta blocker overdose, though it's considered a second-line treatment. In beta blocker poisoning, intravenous glucagon is typically administered as a 5-10 mg bolus over 1-2 minutes, followed by an infusion of 1-5 mg/hour titrated to clinical response 1. This approach works because glucagon activates adenylyl cyclase through a G-protein coupled receptor that bypasses the blocked beta receptors, thereby increasing intracellular cAMP levels and improving cardiac contractility and heart rate.

Key Points to Consider

• Glucagon is particularly useful when the patient shows signs of cardiovascular compromise such as hypotension and bradycardia that hasn't responded to initial treatments like IV fluids and atropine.
• First-line treatments for severe beta blocker overdose now typically include high-dose insulin therapy and vasopressors, with glucagon serving as an adjunctive therapy 1.
• Clinicians should be prepared for the possibility that large doses may be required, and should ensure adequate airway protection as vomiting is a common side effect.
• The recommended dose of glucagon is a bolus of 3 to 10 mg, administered slowly over 3 to 5 minutes, followed by an infusion of 3 to 5 mg/h 1.

Limitations and Side Effects

• Glucagon has limitations including a short duration of action, potential for tachyphylaxis, and side effects like vomiting.
• The amount of glucagon required to sustain this therapy may exceed 100 mg in a 24-hour period, plans should be made early to ensure that an adequate supply of glucagon is available 1.

Clinical Decision Making

• It is reasonable to use a bolus of glucagon, followed by a continuous infusion, for bradycardia or hypotension due to β-blocker poisoning 1.
• High-dose insulin therapy and vasopressors are the first line treatments, with glucagon serving as an adjunctive therapy 1.

From the Research

Glucagon as a Treatment for Beta Blocker Overdose

• Glucagon has been used to reverse beta blocker overdose, with studies showing its effectiveness in increasing heart rate and myocardial contractility, and improving atrioventricular conduction 2, 3, 4.
• The mechanism of action of glucagon is thought to bypass the beta-adrenergic receptor site, allowing it to be effective even in the presence of beta-receptor blocking drugs 2.
• The recommended dose of glucagon for beta blocker overdose is 50 micrograms/kg iv loading dose, followed by a continuous infusion of 1-15 mg/h, titrated to patient response 2.

Efficacy of Glucagon in Reversing Beta Blocker Overdose

• Studies have shown that glucagon can increase heart rate and cardiac output, and reverse second and third degree AV blocks, at least transiently, in animal models of beta blocker overdose 5.
• However, the effect of glucagon on mean arterial pressure and survival rate in animal models of beta blocker overdose is unclear 5.
• A randomized clinical trial found that high-dose glucagon had significant hemodynamic effects, including increased heart rate, systolic blood pressure, diastolic blood pressure, and cardiac output, regardless of beta-blockade 6.

Safety and Side Effects of Glucagon

• Glucagon can cause side effects such as nausea, vomiting, hypokalemia, and hyperglycemia 2, 6.
• The high cost and limited availability of glucagon may be factors precluding its future clinical acceptance 2.
• Glucagon-induced nausea occurred in 80% of participants in a clinical trial, despite ondansetron pretreatment 6.