17. Beta Blocker Overdose

Mechanism

Types of toxicity:

  • Beta-1 blockade: impaired cardiac contractility, bradycardia, AV block.
  • Non-selective beta blockade: cardiac effects as above, but also bronchospasm, hypoglycemia (impaired glycogenolysis and gluconeogenesis).

Drug specific toxicity:

  • Propranolol (non-selective): may behave like TCA with QRS prolongation. Lipid soluble, which enhances brain penetration and, therefore, potentially epileptogenic and/or leads to comatose state.
  • Metoprolol (B1 selective): mostly cardiac effects. Higher doses (>100mg) may also have B2 antagonistic effects.
  • Pindolol (partial agonist): may cause sympathomimetic effects such as tachycardia and hypertension.
  • Sotalol: beta blocker with class III antiarrhythmic effects that increase refractory period by blocking delayed potassium channels in the heart. Can lead to QT prolongation, Torsades de pointes, VF/VT.

Signs and Symptoms

Hypotension, bradycardia, AV block, convulsions, delirium, coma, seizures, respiratory arrest, bronchospasm, hypoglycemia, hyperkalemia. Usually symptomatic within 2 hours of presentation.

Evaluation

  • Exam: monitor for hypotension, bradycardia. Also may present with coma, altered mental status (especially in non-selective beta-blocker ingestion).
  • ECG: look for first degree heart block. High degree AV block, cardiogenic shock, and other conduction disturbances may also occur. ECG usually shows normal QRS, increased PR intervals. QRS widening can occur with massive doses and QTc prolongation leading to ventricular arrhythmias may occur with sotalol ingestion.
  • Labs: check fingerstick glucose, BMP, calcium. Evaluate for possible co-ingestions, especially with other cardiac medications (calcium channel blocker, digoxin, clonidine, etc.). Elevated lactate (>3mmol/L) can be a sign of higher mortality, though this is non-specific.

Management

  • Decontamination: activated charcoal 50 g PO or via NG tube. Consider multiple doses of AC and/or whole bowel irrigation (GoLytely 1-2 L/h via NG tube) if ingested beta blocker is a sustained release preparation. Mixed data on its efficacy; however, considered low harm intervention for potential benefits.
  • Hypotension/bradycardia: IV fluids, atropine (IV 0.5-1mg IV every 5 minutes, up to 0.04mg/kg), although atropine alone is usually not enough for reversal in beta blocker overdose. Consider the following in this order:
    • Glucagon: 5-10 mg IV bolus, repeat every 3-5 minutes if no effect. If effect seen, start 1-5 mg/hour infusion. Often causes vomiting; consider giving ondansetron first. Note that tachyphylaxis may occur with prolonged infusion of glucagon (>24h) and prolonged treatment will become ineffective.
    • Calcium: may assist with inotropy. Give 1g 10% calcium chloride (slow push via central venous catheter), up to total 3g. If no central line, 30mL 10% Ca gluconate (up to total 3g).
    • Vasopressors: epinephrine infusion, start 1-4mcg/min and titrate to MAP 60.
    • Insulin: high-dose insulin can have positive inotropic effects. Start with regular insulin 1U/kg IV and infusion 0.5-1 U/kg/hour titrated upward as needed. Maintain euglycemia with D10 or D50 as needed. Be mindful of potential hypokalemia.
    • Lipid emulsion infusion: may be effective for some lipid-soluble drugs (e.g., propranolol) especially in conjunction with insulin therapy; consult with Poison Control.
  • EKG changes: if there is QRS widening due to high dose beta-blocker mediated Na-channel blockade, push sodium bicarbonate 1-2 mEq/kg IV. If there is concern for QTc prolongation or ventricular arrhythmia, give magnesium sulfate 2g IV and/or Mg infusion.
  • Seizures: IV benzodiazepines are first-line treatment.
  • Bronchospasm: albuterol nebulizers.
  • Hypoglycemia: D50 pushes for immediate reversal, then dextrose infusion for maintenance.
  • Hemodialysis: may be beneficial in severe cases for those that ingested hydrophilic compounds such as atenolol, nadolol, sotalol, and acebutolol. Lipophilic beta-blockers such as metoprolol, propranolol will not be able to be removed via hemodialysis.

Key Points

  • Consider multiple doses of activated charcoal for sustained release preparations.
  • If severe toxicity present, contact Poison Control and consider hyperinsulin/euglycemia protocol or lipid emulsion infusion.

 

Bailey B. Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. Journal of Toxicology: Clinical Toxicology. 2003; 41(5):595-602.

Graudins A, et al. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. British Journal of Clinical Pharmacology. 2016 Mar; 81(3):453-461.