What is the toxic dose of metoprolol (beta blocker) that can lead to an overdose?

Metoprolol Overdose: Toxic Dose and Management

A potentially lethal dose of metoprolol is approximately 7.5 grams, with blood concentrations above 19.8 mg/L associated with fatality. 1 The toxic dose varies based on individual factors, but overdoses exceeding 1 gram should be considered life-threatening and require immediate medical intervention.

Toxic Dose Information

• The oral LD50 in animal studies ranges from 1158-2460 mg/kg in mice and 3090-4670 mg/kg in rats 2
• Case reports document:
  • Fatal overdose with blood concentration of 19.8 mg/L 1
  • Severe toxicity requiring advanced life support after ingestion of approximately 7.5 grams 3
  • Dose-symptom relationship appears linear for metoprolol, unlike other beta-blockers that have threshold toxicity 4

Clinical Presentation of Metoprolol Overdose

Metoprolol overdose primarily affects the cardiovascular system, causing:

• Bradycardia (often severe and refractory)
• Hypotension progressing to cardiogenic shock
• Myocardial depression
• Potential cardiac arrest

Additional manifestations may include:

• Bronchospasm (due to loss of β1-selectivity at high doses)
• Central nervous system depression
• Seizures (less common than with propranolol)

Management of Metoprolol Overdose

Initial Stabilization

1. Secure airway, breathing, and circulation
2. Establish IV access (preferably central venous access)
3. Continuous cardiac monitoring
4. Frequent vital sign assessment

First-Line Treatments

1. High-dose insulin therapy (Class 1, Level B-NR recommendation) 5

   • Initial bolus: 1 U/kg IV regular insulin
   • Maintenance: 0.5-1 U/kg/hour infusion
   • Concurrent dextrose: 0.5 g/kg IV bolus and 0.5 g/kg/hour infusion
   • Monitor glucose every 15 minutes initially

2. Vasopressors for immediate blood pressure support 5

   • Epinephrine or norepinephrine preferred over dopamine
   • Titrate to effect

Second-Line Treatments

1. Glucagon (Class 2a, Level C-LD recommendation) 5

   • Initial dose: 2-10 mg IV bolus
   • Maintenance: 1-15 mg/hour infusion
   • Caution: may cause vomiting (risk of aspiration)

2. Atropine for bradycardia 5

   • 0.5-1.0 mg IV every 3-5 minutes (maximum 3 mg)

3. Calcium for refractory shock (Class 2b, Level C-LD) 5

   • Initial dose: 0.3 mEq/kg IV
   • Maintenance: 0.3 mEq/kg/hour infusion

Refractory Cases

1. VA-ECMO for life-threatening toxicity unresponsive to pharmacological interventions 5

2. Hemodialysis may be considered, though metoprolol is only slightly dialyzable (clearance 80-120 mL/min) 6

   • Only removes approximately 3.3% of ingested dose during a 6-hour treatment 6
   • More effective for atenolol or sotalol overdose

Monitoring

• Continuous cardiac monitoring
• Frequent glucose checks (every 15 minutes initially)
• Regular potassium monitoring (moderate hypokalemia expected with insulin therapy)
• Assessment of mental status and peripheral perfusion
• Arterial blood gases as needed

Important Considerations and Pitfalls

• Co-ingestions significantly increase mortality risk, especially with other cardioactive drugs like calcium channel blockers 4
• Alcohol co-ingestion was present in a documented fatal case 1
• Delayed recognition of toxicity can lead to rapid deterioration
• Avoid Class IA, IC, or III antiarrhythmics as they may worsen cardiac toxicity 5
• Intravenous lipid emulsion therapy is "not likely to be beneficial" (Class 3: No Benefit, Level C-LD) 5, though case reports show some success 3
• Metoprolol's moderate lipophilicity results in significant cardiac toxicity with less CNS effects compared to highly lipophilic agents like propranolol

Early recognition and aggressive management with high-dose insulin therapy and vasopressor support offer the best chance for survival in significant metoprolol overdose.