What is the best first-line treatment for a beta-blocker overdose presenting with bradycardia and hypotension?

Best First-Line Treatment for Beta-Blocker Overdose

Glucagon intravenously is the best first-line treatment for this patient with metoprolol overdose presenting with bradycardia (HR 46) and hypotension (BP 92/50). 1, 2, 3

Rationale for Glucagon as First-Line

The ACC/AHA/HRS guidelines give glucagon a Class IIa recommendation (reasonable to use) for beta-blocker overdose with symptomatic bradycardia and hemodynamic compromise. 1 This recommendation is based on:

• Glucagon bypasses the blocked beta-adrenergic receptors by activating hepatic adenyl cyclase, directly increasing heart rate and myocardial contractility independent of beta-receptor status 1, 4
• Extensive clinical experience documented in numerous case reports and case series showing consistent increases in heart rate during beta-blocker overdose 1
• Rapid onset of action making it ideal for acute presentations 4

Dosing Protocol for Glucagon

• Initial bolus: 3-10 mg IV over 3-5 minutes 1, 3
• Continuous infusion: 3-5 mg/hour (effects are transient without infusion) 1, 3
• Titrate to hemodynamic response 4

Why Not High-Dose Insulin First?

While high-dose insulin therapy also carries a Class IIa recommendation and has superior evidence in animal models, the 2023 AHA focused update and recent consensus statements now position high-dose insulin as first-line for refractory shock 2, 3. The key distinction:

• High-dose insulin is recommended when standard therapies fail or in severe cardiogenic shock 2, 3, 5
• This patient is currently awake and asymptomatic despite abnormal vitals, suggesting she is not yet in refractory shock [@question context@]
• Glucagon has faster onset and simpler monitoring requirements initially 4
• High-dose insulin requires intensive glucose/potassium monitoring (every 15 minutes initially) and mandatory dextrose co-administration 3, 5

Clinical Algorithm for Beta-Blocker Overdose

Initial stabilization:

• Cardiac monitoring, IV access, airway assessment 2
• IV fluid resuscitation for vasodilation 5

First-line pharmacotherapy:

• Glucagon 3-10 mg IV bolus, then 3-5 mg/hour infusion 1, 3

If refractory to glucagon (persistent shock):

• Escalate to high-dose insulin: 1 U/kg bolus, then 1 U/kg/hour infusion 2, 3, 5
• Mandatory co-administration: 0.5 g/kg dextrose bolus and infusion 3
• Monitor glucose every 15 minutes, target 100-250 mg/dL 3

Vasopressor support if needed:

• Norepinephrine or epinephrine (not dopamine, which is less effective) 2, 3

Rescue therapy for refractory cases:

• VA-ECMO for shock refractory to all pharmacological interventions 1, 2, 3

Why Other Options Are Incorrect

Epinephrine drip: Not first-line; reserved for vasopressor support after antidote therapy initiated 2, 3

High-dose insulin therapy: While highly effective, it is positioned as first-line for refractory shock or as an alternative first-line option, but glucagon remains the traditional and more practical initial choice given this patient's current stability 2, 3, 5

Lipid emulsion therapy: Explicitly NOT recommended for beta-blocker poisoning (Class 3: No Benefit) by the 2023 AHA guidelines 3

Critical Monitoring and Pitfalls

With glucagon therapy:

• Monitor for nausea and vomiting (common side effects, concerning if airway protection compromised) 1
• Watch for tachyphylaxis (rapid tolerance development) 1
• Monitor potassium and glucose (though less intensive than with insulin) 6, 4

Common pitfalls to avoid:

• Do not use lipid emulsion - no benefit and may worsen oral overdose by increasing GI absorption 1, 3
• Do not underdose glucagon - standard cardiac arrest doses (1-2 mg) are insufficient; need 3-10 mg 1, 4
• Do not delay escalation to high-dose insulin if glucagon fails within 30-60 minutes 2, 3, 5

Special Consideration for This Case

This patient took multiple medications including lisinopril (ACE inhibitor), which may compound hypotension. [@question context@] The combination of beta-blocker and ACE inhibitor overdose makes aggressive treatment of hypotension critical, but glucagon specifically addresses the beta-blocker component causing bradycardia 1.