Glucagon Dosing for Beta-Blocker Overdose
For beta-blocker overdose with refractory shock or symptomatic bradycardia, administer glucagon 3-10 mg IV bolus over 5 minutes, followed by continuous infusion of 3-5 mg/hour (adults) or 0.03-0.15 mg/kg bolus followed by 0.07 mg/kg/hour infusion (maximum 5 mg/hour) in children.
Adult Dosing
Initial bolus: 3-10 mg IV administered over 5 minutes 1, 2, 1
Continuous infusion: 3-5 mg/hour, titrated to clinical response 1, 2, 1
The 2020 AHA Guidelines for CPR and Emergency Cardiovascular Care provide a Class IIa recommendation (reasonable to administer) for IV glucagon in patients with β-adrenergic blocker overdose who are in refractory shock 3. This recommendation is echoed in the 2018 ACC/AHA/HRS bradycardia guidelines, which specifically address beta-blocker and calcium channel blocker mediated bradycardia 1, 2, 1.
The FDA-approved glucagon labeling does not specifically address beta-blocker overdose dosing, as the approved indications focus on severe hypoglycemia and diagnostic use 4. However, the off-label use for beta-blocker toxicity is well-established in clinical practice guidelines.
Pediatric Dosing
Initial bolus: 0.03-0.15 mg/kg IV (some sources cite 20-30 mcg/kg with maximum 1 mg) 5, 6
Continuous infusion: 0.07 mg/kg/hour (maximum 5 mg/hour) 6
The pediatric dosing is less well-standardized than adult dosing, but the 2005 anaphylaxis guidelines provide specific weight-based recommendations that have been extrapolated to beta-blocker overdose scenarios 5.
Administration Considerations
- Route: Intravenous administration is preferred for beta-blocker overdose, though glucagon can be given IM or SC for hypoglycemia 4
- Reconstitution: Mix 1 mg glucagon powder with 1 mL diluent to achieve 1 mg/mL concentration; use immediately after reconstitution 4
- Timing: Administer as soon as beta-blocker toxicity with hemodynamic compromise is recognized
Critical Monitoring and Supportive Care
Anticipate and manage nausea/vomiting: Glucagon causes significant gastrointestinal side effects due to delayed gastric emptying 5, 6. Consider prophylactic antiemetics (ondansetron), though one study showed 80% of patients still experienced nausea despite pretreatment 7. Have aspiration precautions in place 5.
Monitor glucose and potassium: Glucagon can cause hyperglycemia and hypokalemia 6. One case series found hyperglycemia occurred in 10.4% of administrations 8.
Hemodynamic monitoring: Continuous cardiac monitoring is essential 1, 2. Recent evidence suggests glucagon produces modest hemodynamic effects—a mean heart rate increase of only 4 bpm and median systolic blood pressure increase of 4.5 mmHg in one case series 8, though a randomized trial in healthy volunteers showed more robust effects (13 bpm heart rate increase, 15.6 mmHg systolic BP increase) 7.
Evidence Quality and Clinical Reality
The evidence supporting glucagon use is predominantly low-quality (Class IIa, Level C-LD), based on animal studies, case reports, and small case series rather than controlled trials 1, 3, 2, 1. A 2023 case series of 107 patients found statistically significant but clinically modest improvements in heart rate and blood pressure 8. The 2019 retrospective analysis of 2,967 beta-blocker overdoses found glucagon was used in only 1% of cases, with all patients recovering 9.
Important caveat: Glucagon infusion may be preferable to repeated boluses, as a 2020 randomized trial demonstrated that infusion produced comparable and apparently longer-lasting hemodynamic effects compared to bolus administration 7. One case report specifically emphasized that restoration of normal blood pressure depended on high-dose glucagon infusion after bolus injections failed 10.
Alternative and Adjunctive Therapies
High-dose insulin therapy (1 unit/kg bolus followed by 0.5-1 unit/kg/hour infusion with dextrose and potassium supplementation) is also reasonable and may be more effective than glucagon 1, 3, 2, 1. The 2020 AHA guidelines give both glucagon and high-dose insulin Class IIa recommendations 3.
Do not combine glucagon with dopamine: An experimental study demonstrated that glucagon/dopamine combination significantly reduced survival time in propranolol-intoxicated rats due to ventilation/perfusion mismatch 11.
Consider ECMO for shock refractory to pharmacological therapy (Class IIb recommendation) 3.