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

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From the Guidelines

Glucagon is a reasonable treatment for bradycardia or hypotension due to beta-blocker poisoning, administered as a bolus followed by a continuous infusion. For the management of beta-blocker overdose, the most recent guidelines from the American Heart Association, as outlined in the 2023 update 1, provide recommendations for various treatment strategies. When considering the use of glucagon, it is essential to understand its role in the context of beta-blocker toxicity. The recommended approach, based on the latest evidence, is to use glucagon as a bolus, followed by a continuous infusion, for bradycardia or hypotension due to beta-blocker poisoning, as stated in the guidelines 1. Key points to consider when administering glucagon include:

  • The dose and administration protocol, which may vary based on patient response and clinical guidelines
  • Potential side effects, such as nausea, vomiting, and hyperglycemia
  • The importance of monitoring glucose levels during prolonged therapy to avoid hypoglycemia
  • Ensuring an adequate supply of glucagon, as high doses may be required Given the potential benefits and the recommendation from the 2023 American Heart Association guidelines 1, glucagon should be considered as part of the treatment strategy for beta-blocker overdose, particularly when patients exhibit bradycardia or hypotension. It is crucial to weigh the potential benefits of glucagon against other treatment options, such as high-dose insulin, vasopressors, and extracorporeal life support techniques, as outlined in the guidelines 1. Ultimately, the decision to use glucagon should be based on the individual patient's clinical presentation and response to initial treatments, with the goal of optimizing outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

DRUG INTERACTIONS Beta-blockers: Patients taking beta-blockers may have a transient increase in pulse and blood pressure.

The role of glucagon in beta-blocker overdose is to potentially increase pulse and blood pressure. However, the label does not provide explicit guidance on the use of glucagon in the setting of a beta-blocker overdose.

  • Key consideration: The FDA label does not provide direct information on the use of glucagon for treating beta-blocker overdose.
  • Clinical decision: In the absence of explicit guidance, glucagon may be considered as a potential treatment for beta-blocker overdose due to its effects on increasing pulse and blood pressure, but this should be done with caution and under medical supervision 2.

From the Research

Role of Glucagon in Beta-Blocker Overdose

  • Glucagon is considered as an alternative therapy for profound beta-blocker intoxications, as its mechanism of action may bypass the beta-adrenergic receptor site 3.
  • Glucagon increases heart rate and myocardial contractility, and improves atrioventricular conduction, which are unchanged by the presence of beta-receptor blocking drugs 3.
  • The doses of glucagon required to reverse severe beta-blockade are 50 micrograms/kg iv loading dose, followed by a continuous infusion of 1-15 mg/h, titrated to patient response 3.
  • Glucagon-treated patients should be monitored for side effects of nausea, vomiting, hypokalemia, and hyperglycemia 3.

Evidence from Systematic Reviews

  • A systematic review found that glucagon appeared to consistently increase the heart rate at least transiently in animal models of beta-blocker overdose, but its effect on mean arterial pressure and survival rate was unclear 4.
  • Another systematic review found that glucagon was associated with minor improvements in haemodynamics through an increase in heart rate in two case series, nine case reports, and five animal studies 5.

Comparison with Other Treatments

  • Glucagon is considered as a first-line antidote for beta-blocker poisoning with symptomatic bradycardia and hypotension, while high-dose insulin with supplemental dextrose and potassium therapy (HDIDK) is reserved for refractory cases of calcium channel blocker poisoning 6.
  • In cases of concurrent beta-blocker and calcium channel blocker overdose, high-dose insulin infusion and lipid emulsion therapy may be used in addition to glucagon and calcium salts 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Glucagon therapy for beta-blocker overdose.

Drug intelligence & clinical pharmacy, 1984

Research

Treatment for beta-blocker poisoning: a systematic review.

Clinical toxicology (Philadelphia, Pa.), 2020

Research

Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2006

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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