What is the recommended reverse agent for beta blocker overdose or toxicity?

Reversal Agent for Beta-Blocker Overdose

For life-threatening beta-blocker overdose with refractory hypotension or bradycardia, high-dose insulin euglycemia therapy is the first-line reversal agent, with glucagon as an equally reasonable alternative. 1

First-Line Reversal Agents

High-Dose Insulin Euglycemia Therapy (Preferred)

• Administer 1 U/kg regular insulin IV bolus with simultaneous 0.5 g/kg dextrose bolus, followed by continuous infusion of 1 U/kg/hour insulin and 0.5 g/kg/hour dextrose. 1
• High-dose insulin improves myocardial contractility and hemodynamic stability with lower rates of vasoconstrictive complications compared to vasopressor-only therapy. 1
• Monitor serum glucose every 15 minutes initially, then hourly once stable, targeting 100-250 mg/dL. 1
• Monitor potassium levels closely as hypokalemia can occur. 1
• Concentrated dextrose solutions (>10%) require central venous access. 1

Glucagon (Equally Reasonable First-Line)

• Administer 3-10 mg IV bolus over 3-5 minutes, followed by continuous infusion of 3-5 mg/hour. 1
• Glucagon bypasses blocked beta-receptors by directly activating adenyl cyclase, increasing heart rate and contractility independent of beta-receptor status. 1, 2
• Titrate infusion to achieve adequate mean arterial pressure and perfusion. 1
• May require >100 mg in 24 hours; ensure adequate supply is available early. 1
• Critical caveat: Glucagon commonly causes vomiting—protect the airway before administration in patients with altered mental status. 1

Second-Line Therapies

Vasopressors

• Administer vasopressors (norepinephrine or epinephrine) for persistent hypotension. 1, 3
• Norepinephrine increases blood pressure in vasoplegic shock; epinephrine increases contractility and heart rate. 3
• Beta-blocker overdose may cause such severe receptor inhibition that high-dose vasopressors cannot effectively restore hemodynamics, necessitating the reversal agents above. 1

Calcium

• Consider IV calcium (calcium chloride 10-20 mL of 10% solution or calcium gluconate 10-30 mL of 10% solution over 5-10 minutes) for refractory shock. 1
• Evidence is weaker for beta-blocker overdose compared to calcium channel blocker toxicity. 2
• Monitor ionized calcium levels during infusions. 4

Atropine and Pacing

• Atropine may be reasonable for beta-blocker-induced bradycardia, though evidence is limited. 1
• Electrical pacing may be reasonable for refractory bradycardia. 1

Rescue Therapy for Refractory Cases

VA-ECMO

• Consider VA-ECMO for life-threatening beta-blocker poisoning with cardiogenic shock refractory to maximal pharmacological interventions. 1, 3
• Case reports and observational studies suggest VA-ECMO may be life-saving for persistent pump failure. 1

Hemodialysis (Specific Beta-Blockers Only)

• Hemodialysis may be reasonable for life-threatening atenolol or sotalol poisoning (hydrophilic beta-blockers). 1
• Not effective for lipophilic beta-blockers (propranolol, metoprolol). 5

Treatment Algorithm

1. Immediate stabilization: Establish cardiac monitoring, secure IV access, assess and protect airway. 1, 3
2. First-line pharmacotherapy: Initiate high-dose insulin euglycemia therapy OR glucagon bolus and infusion. 1, 3, 2
3. Concurrent vasopressor support: Add norepinephrine or epinephrine if hypotension persists. 1, 3
4. Second-line therapy: Consider IV calcium for refractory shock. 1, 3
5. Rescue therapy: Consult for VA-ECMO if shock remains refractory to all pharmacological interventions. 1, 3

Critical Pitfalls to Avoid

• Do not use intravenous lipid emulsion therapy—it is not likely to be beneficial for beta-blocker poisoning. 1
• Do not underdose glucagon; standard doses used for hypoglycemia (1-2 mg) are inadequate for beta-blocker overdose. 2, 6
• Do not delay escalation to high-dose insulin if glucagon is ineffective within 30-60 minutes. 2
• Do not administer flumazenil in undifferentiated coma—it is contraindicated and may precipitate seizures. 1
• Avoid abrupt withdrawal of beta-blocker therapy in patients on chronic therapy, as it can cause clinical deterioration. 3

Special Monitoring Considerations

• Continuous cardiac telemetry for rhythm and conduction abnormalities. 4
• Arterial line for continuous blood pressure monitoring in shock states. 4
• Serial glucose and potassium monitoring (every 15 minutes initially with high-dose insulin). 1, 4
• Monitor for tachyphylaxis with glucagon therapy. 2
• Consider early consultation with medical toxicology or poison control center (1-800-222-1222). 4