What is the drug of choice for beta blocker (beta-adrenergic blocking agent) overdose reversal?

Drug of Choice for Beta Blocker Reversal

High-dose insulin with glucose supplementation is the drug of choice for beta blocker overdose with refractory hypotension, receiving the highest level recommendation (Class 1, Level B-NR) from the 2023 American Heart Association guidelines. 1

Treatment Algorithm for Beta Blocker Overdose

First-Line Therapy: Vasopressors

• Initiate vasopressors immediately for hypotension due to beta blocker poisoning (Class 1, Level C-LD), as they are readily available and act quickly 1
• Vasopressors serve as the initial therapy while preparing definitive antidotal treatment 1

Primary Antidote: High-Dose Insulin

• Administer high-dose insulin for hypotension refractory to or in conjunction with vasopressor therapy (Class 1, Level B-NR) 1
• High-dose insulin improves myocardial inotropy in cardiogenic shock from beta blocker poisoning and demonstrates favorable outcomes with lower rates of vasoconstrictive complications compared to vasopressor-only therapy 1

Dosing Protocol:

• Initial bolus: 1 U/kg regular insulin IV 1, 2
• Accompanied by: 0.5 g/kg dextrose bolus 1, 2
• Continuous infusion: 0.5-1 U/kg/hour insulin 1, 2
• Continuous dextrose: 0.5 g/kg/hour 1, 2

Critical Monitoring Requirements:

• Glucose monitoring every 15 minutes initially, targeting 100-250 mg/dL (5.5-14 mmol/L) 2, 3
• Potassium monitoring is essential as insulin causes intracellular potassium shift 2, 3
• Target potassium levels: 2.5-2.8 mEq/L to avoid aggressive repletion 2, 3

Secondary Antidote: Glucagon

• Use glucagon as a reasonable alternative for bradycardia or hypotension due to beta blocker poisoning (Class 2a, Level C-LD) 1
• Glucagon increases contractility and improves hemodynamics by activating hepatic adenylate cyclase, bypassing the blocked beta-adrenergic receptors 1, 2

Dosing Protocol:

• Initial bolus: 3-10 mg IV administered slowly over 3-5 minutes 1, 2
• Continuous infusion: 3-5 mg/hour (0.05-0.15 mg/kg followed by 0.05-0.10 mg/kg/hour) 1, 2
• Titrate infusion to achieve adequate hemodynamic response 1

Important Caveats:

• Glucagon commonly causes vomiting; protect the airway before administration in patients with CNS depression 1
• May require >100 mg in 24 hours; ensure adequate supply is available early 1
• Concomitant use with dopamine, isoproterenol, or milrinone may decrease glucagon effectiveness 1

Tertiary Options

Calcium:

• May be considered for refractory shock (Class 2b, Level C-LD) 1
• Limited animal data and rare case reports suggest possible utility 1
• Dose: 1-2 g of 10% calcium chloride every 10-20 minutes or infusion of 0.2-0.4 mL/kg/hour 2

Atropine:

• May be reasonable for beta blocker-induced bradycardia (Class 2b, Level C-LD) 1
• Often ineffective due to the mechanism of beta blocker toxicity 1

Rescue Therapy for Refractory Cases

VA-ECMO:

• Reasonable to utilize for life-threatening beta blocker poisoning with cardiogenic shock refractory to pharmacological interventions (Class 2a, Level C-LD) 1
• May be life-saving based on case reports, case series, and observational studies 1

Hemodialysis:

• May be reasonable specifically for life-threatening atenolol or sotalol poisoning (Class 2b, Level C-LD) 1
• These agents are more dialyzable than other beta blockers 1

What NOT to Use

Intravenous Lipid Emulsion (ILE):

• Not likely to be beneficial for life-threatening beta blocker poisoning (Class 3: No Benefit, Level C-LD) 1
• This represents a significant departure from earlier practices and should be avoided 1

Key Clinical Pitfalls

• Do not delay high-dose insulin therapy in refractory hypotension—it has the strongest evidence base and highest recommendation level 1
• Ensure adequate glucose and potassium monitoring when using insulin; hypoglycemia and hypokalemia are preventable complications with proper monitoring 2, 3
• Recognize that standard vasopressor doses may be inadequate due to severe beta-receptor inhibition; high-dose insulin addresses this by improving myocardial energy utilization rather than relying on receptor activation 1
• Treat hypoglycemia with supplemental dextrose as part of standard care, as beta blocker poisoning is sometimes associated with hypoglycemia 1