When should glucagon be initiated in a beta‑blocker overdose patient who develops symptomatic bradycardia (heart rate <50 bpm) with hypotension (systolic <90 mm Hg) or signs of poor perfusion despite adequate fluid resuscitation and atropine?

Glucagon Therapy Initiation in Beta-Blocker Overdose

Initiate glucagon immediately when a beta-blocker overdose patient develops symptomatic bradycardia (HR <50 bpm) with hypotension (SBP <90 mmHg) or signs of poor perfusion that persists despite adequate fluid resuscitation and atropine, as glucagon is a reasonable treatment option (Class IIa recommendation) that can be administered while preparing high-dose insulin therapy. 1, 2

Treatment Algorithm for Beta-Blocker Overdose

Initial Stabilization

• Begin with intravenous fluid resuscitation to correct vasodilation and low cardiac filling pressures 3
• Administer atropine for bradycardia, though recognize it is often ineffective due to the mechanism of beta-blocker toxicity (Class 2b recommendation) 2, 3

When to Start Glucagon

Glucagon should be initiated when:

• Heart rate remains <50 bpm with hemodynamic compromise after atropine 2
• Systolic blood pressure is <90 mmHg with signs of poor perfusion 2
• The patient demonstrates cardiogenic shock features despite initial supportive measures 1, 3

Glucagon Dosing Protocol

• Initial bolus: 3-10 mg IV administered over 3-5 minutes 1, 2
• Continuous infusion: 3-5 mg/hour immediately following the bolus, as glucagon's effects are transient 1, 2
• The infusion is essential because the hemodynamic benefits of glucagon are short-lived 1

Mechanism and Expected Response

• Glucagon counteracts beta-blocker effects by activating hepatic adenylate cyclase, which bypasses the blocked beta-adrenergic receptors 1, 2, 4
• This increases myocardial contractility and improves atrioventricular conduction independent of beta-receptor activity 4
• Monitor for increased heart rate and improved blood pressure within minutes of administration 5, 4

Critical Pitfalls and Limitations

Glucagon Is Not First-Line Therapy

High-dose insulin is superior to glucagon and should be considered the definitive treatment for refractory beta-blocker overdose. 2, 3, 6

• The American Heart Association gives high-dose insulin the highest recommendation (Class 1, Level B-NR) for refractory hypotension 2
• Animal studies demonstrate high-dose insulin is superior to glucagon in terms of survival and hemodynamic improvement 3
• If glucagon fails to improve hemodynamics within 30-60 minutes, immediately escalate to high-dose insulin (1 U/kg bolus, then 1-10 U/kg/hour infusion with glucose supplementation) 2, 3, 6

Glucagon Side Effects

• Nausea and vomiting are common and particularly concerning when airway protection is compromised 1
• Consider early airway management if the patient's mental status is altered 1
• Monitor for hyperglycemia and hypokalemia during therapy 4

Vasopressor Considerations

• Vasopressors should be initiated immediately for hypotension, as they are readily available and act quickly (Class 1, Level C-LD) 2
• However, catecholamines increase systemic vascular resistance, which may paradoxically decrease cardiac output and organ perfusion 3
• The increased myocardial oxygen demand from vasopressors can be deleterious in the setting of decreased coronary perfusion 3

When Glucagon Is Insufficient

Escalation to High-Dose Insulin

• If hemodynamics do not improve with glucagon within 30-60 minutes, immediately initiate high-dose insulin 2, 3, 6
• Dosing: 1 U/kg bolus followed by 1-10 U/kg/hour continuous infusion 2, 3, 6
• Mandatory coadministration of dextrose and potassium supplementation 2, 3
• One case report demonstrated dramatic hemodynamic improvement only after reaching 10 U/kg/hour insulin, with three of five vasopressors weaned within 8 hours 6

Rescue Therapies for Refractory Cases

• VA-ECMO for cardiogenic shock refractory to pharmacological interventions (Class 2a, Level C-LD) 2, 7
• Temporary transvenous pacing for persistent symptomatic bradycardia unresponsive to pharmacotherapy 2, 8
• Hemodialysis specifically for life-threatening atenolol or sotalol poisoning (Class 2b, Level C-LD) 2, 7

What NOT to Use

• Intravenous lipid emulsion is not beneficial for beta-blocker poisoning (Class 3: No Benefit) 2, 7

Monitoring Requirements

• Continuous cardiac monitoring for bradycardia and conduction disturbances 2, 8
• Frequent glucose and potassium monitoring during glucagon and insulin therapy 2, 3
• Early echocardiography to detect subclinical myocardial dysfunction 8
• Serial lactate measurements to assess tissue perfusion 9