INDEX

    Beta Blockers Overdose

    Cardiovascular, Toxicology

    Last Updated Oct 20, 2020
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    Context

    • Beta blockers are primarily prescribed for their antihypertensive, negative chronotropic and antianginal effects. They are also used for cardiac dysrhythmias, congestive heart failure, migraine prophylaxis, and glaucoma.

    Signs and Symptoms

    • Common: bradycardia, hypotension and cardiovascular collapse.
      • Most common in patients who have co-ingested other cardiac agents (e.g. calcium channel blockers, digoxin) or who have underlying cardiac disease.
    • Less common: CNS effects including coma and seizures may be seen.
    • Uncommon: Ventricular dysrhythmias.

    Laboratory abnormalities

    • Hypoglycemia rare. Hyperglycemia may occur transiently.

    ECG changes can include

    • Bradycardia.
    • AV Block (all levels).
    • QT prolongation with some agents (sotolol).
    • QRS prolongation by agents with membrane stabilizing effects (acebutolol, propranolol).

    Mechanism of Toxicity

    1. Beta-1 adrenergic antagonism reduces heart rate, conduction velocity and contractility.
    2. Non-selective beta blockers also antagonize beta-2 receptors, causing bronchoconstriction, however, this is rare.
    3. Membrane stabilizing effects (sodium channel blockade) of propranolol and acebutolol, can result in QRS prolongation, reduced contractility, and ventricular dysrhythmias.
    4. Alpha adrenergic blocking activity of carvedilol and labetalol may result in pronounced hypotension through peripheral vasodilation.
    5. Potassium channel blocking effects of sotalol can result in QTc interval prolongation.

     

    Toxic Dose

    Diagnostic Process

    • Serum levels for beta blockers are not readily available.
    • All patients should have basic toxicological investigations (ECG, electrolytes, salicylates, acetaminophen, ethanol, and digoxin level where appropriate).

    Clinical Pitfalls

    • Failure to recognize additional toxicity of some beta blockers (propranolol, acebutolol, sotalol).
    • Managing patients with coingestions of other cardiotoxic drugs and/or pre-existing cardiac disease.

    Recommended Treatment

    Can be very complex – consult BC DPIC early.

    • Asymptomatic patients
      • Immediate release preparation (except sotalol): monitor vital signs and continuous cardiac monitoring for at least 6 hours post ingestion.
      • Sustained release preparation ingestion or sotalol: monitor at least 12 hours.
      • ECG should be obtained on admission and prior to discharge.
    • Symptomatic patients
      • Monitor until symptoms resolve.
      • Consider gastric lavage within the first hour following massive ingestion.
      • Administer activated charcoal within the first 2-4 hours of ingestion.
      • Whole bowel irrigation consider with ingestion of sustained release preparations.
    • Treatment of bradycardia and hypotension may involve different therapies that may need to be started simultaneously
      • Atropine.
      • IV fluids.
      • Vasopressors: Norepinephrine is the initial agent. Dopamine can be used alternatively. Titrate to effect as very high doses may be required; Start at 0.1 mcg/kg/min (7-10 mcg/min) and titrate up rapidly. Epinephrine (0.1 mcg/kg/min to start) or Vasopressin (2.4 units/hour fixed dose) are reasonable second line agents.
      • High-dose insulin (HDI) therapy improves cardiac function without increasing myocardial work. Early initiation of HDI therapy (start when vasopressors are started)is recommended as response may take 30-90 minutes. Start with 1 unit/kg insulin bolus with 50 mL D50W, followed by a continuous infusion of 1 unit/kg/hour, titrating by 0.5-1 unit/kg/hour every 20-30 minutes to achieve a systolic blood pressure of 90-100 mm Hg). Intravenous dextrose should be infused at 0.5 g/kg/h (Usually D10W at 100-200 mL/h).
      • Glucagon may improve bradycardia and hypotension and should be given early in treatment. Consider early addition to other therapies (e.g. HDI) as clinical effects of glucagon is transient, hospital supplies are usually limited, and glucagon may induce vomiting. Start with 3-10 mg bolus (0.05-0.15 mg/kg in children) followed by infusion.
      • Lipid emulsion therapy (LET) (Intralipid ®) may be considered in patients with cardiac arrest or cardiovascular collapse unresponsive to therapies listed above. Provide an initial bolus of 1.5 mL/kg IV of 20% lipid emulsion over 1 minute. In asystolic patients, bolus can be repeated twice at 5-minute intervals. This can be followed by an infusion of 20% lipid emulsion (Intralipid®) at 0.25 – 0.5 mL/kg/minute for 30-60 minutes. LET is NOT a first-line therapy.
    • Other measures to consider, if not responding, include
      • Calcium may improve blood pressure but not heart rate. Calcium chloride is preferred over calcium gluconate (3 times more concentrated) but should not be given peripherally. Dose: Adult: 10-20 mL of 10% calcium chloride, or 30-60 mL of 10% calcium gluconate.
      • Phosphodiesterase inhibitors such as milrinone (0.125-0.250 mcg/kg/min) may be useful but use is often limited by vasodilation which can worsen hypotension.
      • Non-pharmacologic therapies:
        • Transvenous pacing is usually ineffective.
        • Extra corporeal membrane oxygenation (ECMO) can be considered in severe overdoses not responding to high dose insulin and/or LET. Early consultation or referral/transfer to an ECMO center may be appropriate.
    • Further specific measures may be beneficial
      • Ventricular dysrhythmias not responding to correction of bradycardia:
        • Sodium bicarbonate boluses for QRS widening or ventricular dysrhythmias.
        • IV magnesium sulfate or overdrive pacing for treatment of torsades de pointes in sotalol poisoning; lidocaine may also be effective.
      • Bronchospasm = inhaled beta-2 bronchodilators.
      • Seizures = IV benzodiazepines.
      • Hypoglycemia = IV dextrose.
      • Renal failure or correction of refractory metabolic acidosis = hemodialysis. Hemodialysis has been reported to remove nadolol, acebutolol, sotolol and atenolol (NASA nemonic).

    Criteria For Transfer To Another Facility

    Consult

    Criteria For Safe Discharge Home

    • After observation periods have been met and the patient’s psychiatric condition has been treated if the overdose was intentional.

    Quality Of Evidence?

    Justification

    Case Reports and Case Series.

    Low

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