What is the toxic dose of metoprolol (beta blocker)?

Toxic Dose of Metoprolol

The toxic dose of metoprolol varies by individual, but ingestions exceeding 1 gram can cause severe toxicity, with fatalities reported at doses of 5-7.5 grams, especially when combined with other cardioactive substances or alcohol. 1, 2

Dose-Toxicity Relationship

• Metoprolol shows a linear dose-symptom relationship, with severity of symptoms increasing proportionally to the ingested amount 3
• Oral LD50 in animal studies ranges from 1158-2460 mg/kg in mice and 3090-4670 mg/kg in rats 2
• Case reports document severe toxicity with ingestions of approximately 7.5 grams of metoprolol tartrate 4
• Fatal overdoses have been associated with blood metoprolol concentrations of 19.8 mg/L (therapeutic range: 0.035-0.5 μg/mL) 5, 6

Clinical Manifestations of Toxicity

• Cardiovascular effects typically appear within 2 hours of ingestion for immediate-release formulations and within 8 hours for sustained-release formulations 1
• Primary manifestations include:
  • Bradycardia and heart block 1, 2
  • Hypotension and cardiogenic shock 1, 2
  • Myocardial depression 4
  • Cardiac arrest in severe cases 4
• Additional manifestations may include:
  • Bronchospasm 2
  • Altered mental status 1
  • Hyperkalemia and hypoglycemia 1

Risk Factors for Increased Toxicity

• Co-ingestion with other cardioactive drugs (especially calcium channel blockers) significantly increases mortality risk 1, 3
• Alcohol co-ingestion potentiates toxicity 3, 5
• Poor CYP2D6 metabolizer status can lead to zero-order elimination kinetics and prolonged toxicity even with therapeutic dosing 6
• Pre-existing cardiac disease, especially recent myocardial infarction, increases vulnerability to hemodynamic instability 2

Management of Metoprolol Toxicity

• For bradycardia:

  • Administer atropine 4
  • Consider temporary cardiac pacing for refractory bradycardia 3
  • Glucagon (5-10 mg IV bolus followed by 1-5 mg/hour infusion) may improve heart rate 1

• For hypotension:

  • Administer IV fluid boluses (10 mL/kg of normal saline) 2
  • Vasopressors: norepinephrine and epinephrine are more effective than dopamine 1, 2
  • High-dose insulin euglycemia therapy (up to 10 U/kg/hour) has shown efficacy in severe cases 4, 6

• For severe toxicity:

  • Intravenous lipid emulsion therapy may be beneficial, especially for lipophilic beta-blockers like metoprolol 4
  • Consider extracorporeal life support (ECLS) for refractory shock 1
  • Gastric decontamination with activated charcoal if within 1-2 hours of ingestion 3

Monitoring and Supportive Care

• Continuous cardiac monitoring with frequent blood pressure checks 7
• Monitor for signs of worsening heart failure and bronchospasm 7
• Assess renal and hepatic function as severe toxicity can lead to organ failure 6
• Therapeutic drug monitoring has limited utility as concentrations correlate poorly with clinical effects 1

Special Considerations

• The American Heart Association recommends a maximum IV dose of 15 mg (three 5 mg boluses) for therapeutic use, highlighting the narrow therapeutic window 7
• Metoprolol's moderate lipophilicity (compared to highly lipophilic propranolol) affects its toxicokinetics and treatment approach 4
• Recovery from severe toxicity may take 24-36 hours even with appropriate interventions 4, 6