Beta-Blocker

Pathophysiology

Complications following beta blocker overdose are related to the excessive beta-adrenergic blockade, the proarrhythmic activity of these agents, and lipophilicity:

• Beta-adrenergic receptors

  Beta-1 (Cardiac muscle):

  • Increased inotropy, chronotropy, and automaticity in the heart

  Beta-2 (Bronchial smooth muscle and peripheral vascular smooth muscle):

  • Bronchodilation

  • Vasodilation

  • Enhanced gluconeogenesis and potassium movement into cells

  Beta-3 (Cardiac muscle and adipose tissue):

  • Reduce cardiac contractility

  • Catecholamine-induced thermogenesis

• Membrane Stabilizing Activity (MSA)

  Membrane Stabilizing Activity (MSA):

  Agents such as propranolol and acebutolol inhibit myocardial fast sodium channels which can cause widened QRS intervals and potentiate other dysrhythmias.

• Lipophilicity:

  Beta-blockers with high lipid solubility (e.g. Propanolol) can easily cross the blood-brain barrier and may cause various central nervous system (CNS) manifestations such as seizures and delirium.

Presentation

• Bradycardia

• Bronchospasm

• Hypotension

• Hypoglycemia

• Hyperkalemia

• Widened QRS, ventricular arrhythmias, and prolonged QTc

• Seizures, coma

Diagnosis

Consult Poison Control: 1800-222-1222

Obtain blood gas, lactate, CMP, EKG, and screen for co-ingestions

1. What type of product was ingested (immediate vs. sustained release)?

2. Any presence of synergistic co-ingestants (calcium channel blockers, TCAs, antipsychotics)?

3. Any underlying cardiovascular disease that could be particularly vulnerable to beta-blocker toxicity?

Management

• ABCs

  A: Due to risk for CNS depression, prompt management of airway is crucial.

  • Premedication with atropine should be given early as laryngeal manipulation may cause vagal stimulation and worsened bradycardia.

  B: Risk of bronchospasm due to beta-blockade.

  • Treat with albuterol and supplemental oxygen.

  C: High risk of symptomatic bradycardia and hypotension

  • IV normal saline bolus

  • IV Atropine (0.5 to 1 mg every three to five minutes up to a total of 0.03 to 0.04 mg/kg).

  • Sodium bicarbonate for QRS widening and magnesium for QTc prolongation

• Gastric decontamination

  Activated charcoal

  (1 g/kg; max 50 g) in all patients who present within two hours of suspected ingestion

  Gastric lavage and/or whole bowel irrigation

  Reserved for patients who have ingested large quantities of sustained release or enteric coated preparations.

Additional treatments for refractory hypotension and bradycardia:

• Glucagon: Bolus: 0.15 mg/kg IV (max 10 mg) x 3 | Infusion: 0.15 mg/kg/h IV (max 5 mg/hr)

  Glucagon has positive inotropic and chronotropic effects on the myocardium by increasing cAMP concentration through a non-adrenergic mechanism

  If positive response, start a continuous infusion to maintain a MAP >60

• Calcium chloride 20 mg/kg (maximum dose is 1 g) | Calcium gluconate 60 mg/kg per dose (maximum dose is 3 g)

  Acts by increasing inotropy

• Epinephrine: 0.1 mcg/kg/min, titrate by 0.05 - 0.2 mcg/kg/min q10-15 min (max 1 mcg/kg/min)

  Catecholamines have positive inotropic and chronotropic effects on the myocardium by stimulating adrenergic receptors and increasing the concentration of cAMP. Any vasopressors should be started in extreme caution given possibility of ineffective response or clinical deterioration secondary to beta blockade.

• Insulin & Dextrose: Insulin 1U/kg/hr IV titrated based on BP response | D10W 5 mL/kg/hr (max 250 mL/hr) and titrated based on blood glucose

  Improves inotropy by increasing glucose and lactate uptake by myocardial cells to overcome metabolic starvation in the heart. The inotropic effect of insulin may be delayed up to 60 min, so supportive treatments with vasopressors may be needed in the interim

• Intralipid 20% emulsion (ILE): 1.5 mL/kg bolus | Infusion: 0.25 mL/kg/min for 30–60 min

  Lipid emulsion surround lipophilic drug molecules and renders them ineffective. Fatty acids provide the myocardium with a ready energy source, thereby improving cardiac function.

Monitoring:

Asymptomatic patients without the need for further interventions can be discharged after a six-hour period of observation. Patients who have ingested an extended-release preparation, sotalol, or multiple cardioactive agents should be observed for 24 hours even if they are asymptomatic.

References

1.     American Academy of Pediatrics. Poisoning. In: McInerny TK, Adam HM, Campbell DE, DeWitt TG, Foy JM, Kamat DM, eds. American Academy of Pediatrics Textbook of Pediatric Care. American Academy of Pediatrics; 2017;

2.     Khalid MM, Galuska MA, Hamilton RJ. Beta-Blocker Toxicity. [Updated 2020 Nov 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448097/

3.     Wax P, et al.  β-Blocker Ingestion: An Evidence-Based Consensus Guideline for Out-of-Hospital Management, Clinical Toxicology, 43:3, 131-146, DOI: 10.1081/CLT-62475