Beta-Blocker Overdose

Updated 2nd July 2024

OVERVIEW

• Most ingestions are benign, exceptions include:
  • overdoses in the elderly and those with decreased cardio-respiratory reserve
  • co-ingestions of other cardiovascularly active agents (especially negative inotropes)
  • severe beta blocker overdoses
• Two beta-blockers require special consideration:
  • propanolol causes sodium channel blockade
  • sotalol causes potassium efflux blockade

TOXICODYNAMICS

• competitive antagonism of beta-1 and beta-2 receptors (selectivity may vary with type of beta blocker and dose)
  • decreased production of intracellular cyclic adenosine monophosphate (cAMP)
  • impairs the many metabolic and cardiovascular effects of circulating catecholamines.
  • used in therapeutic doses to decrease heart rate and blood pressure.
  • in overdose causes increasing severe negative effects on chrontropy, dromotropy, and inotropy leading to cardiac failure and cardiogenic shock.
  • Utilising glucose instead of fatty acids which produce less ATP, may exacerbate the cardiac effects.
• Propranolol also causes sodium channel blockade, widening the QRS and promoting ventricular dysrhythmias and enters the CNS to exert direct toxicity.
• Sotalol also blocks cardiac potassium efflux channels causing QT prolongation and the risk of torsades de pointes.

TOXICOKINETICS

• Rapid absorption (slower if modified release formulation)
• Peak serum concentration usually 1 – 3h
• Propranolol is extremely lipophilic
• Elimination half lives vary and are extended in overdose. Propanol is normally ~12h.

RISK ASSESSMENT

Onset

• onset of effects usually within 1-2 hours
• onset may be delayed following metoprolol MR ingestion

Propanolol

• Propanolol >1-2g oral ingestion is likely to cause significant toxicity, with onset <6 hours

Patient factors

• worse toxicity expected if:
  • elderly
  • cardio-respiratory comorbidities
  • on regular, or co-ingested with, cardiovascularly active agents (especially negative inotropes)

General clinical features

• CVS: hypotension, negative dromotropy (progress AV block – PR prolongation may be the first sign of beta blocker toxicity) and negative chronotropy (bradycardia), heart failure (including pulmonary oedema), cardiovascular collapse
• RESP: bronchospasm (e.g. if coexistent asthma)
• METABOLIC: hypoglycaemia, hyperkalaemia
• NEURO: stupor, coma (usually secondary to hypotension)

Propanolol (“sodium channel blocker masquerading as a beta blocker”)

• CVS: QRS prolongation, ventricular arrhythmias, cardiac arrest
• NEURO: delirium, coma, seizures (usually within first 2 hours)

Sotalol

• QT prolongation and Torsades des Pointes (TdP)

MANAGEMENT

Resuscitation

• Bradycardia
  • Atropine 0.01 – 0.03 mg/kg IV (temporising)
  • Adrenaline 10-20 mcg bolus (child 0.1 mcg/kg) q2-3 min until adequate perfusion, then consider infusion: e.g. Adrenaline 0.15mg/kg in 50ml D5W at 1-10ml/h IV (0.05 – 0.5 mcg/kg/min).
  • Isoprenaline 1 – 10 micrograms/min IV infusion (0.05-1.0 microgram/kg/min in children) (may exacerbated hypotension through B2 effects, especially if ingestant is B1-specific beta blocker)
  • Electrical pacing – transcutaneous pacing is often ineffective, however transvenous pacing may provide definitive therapy if pharmacological therapy fails
• Hypotension (requires a graduated approach)
  • 20ml/kg IV crystalloid bolus (beware of pulmonary oedema if considering repeated fluid boluses)
  • Adrenaline first line if bradycardic and hypotensive as described above
  • If refractory to adrenaline, assess for evidence of bradycardia (see above), poor cardiac contractility, and vasodilation
    • Poor cardiac contractility – treat with High dose Insulin Euglycaemic Therapy (HIET) (see High-dose Insulin Euglycaemic Therapy)
      • acts as an inotrope, lacks a chronotropic effect and may cause vasodilation
      • complications of hypoglycaemia and hypokalaemia from HIET may be more likely when used for beta blocker toxicity than when used for calcium channel blocker toxicity.
    • Vasodilation (aka vasoplegia) – treat with noradrenaline, e.g. 0.15mg/kg in 50ml D5W at 1-10ml/h IV (0.05 – 0.5 mcg/kg/min); consider other vasopressors if refractory vasoplegia.
    • If refractory to fluids, catecholamines, and HIET, with evidence of cardiogenic cause of hypotension the consider extracorporeal life support (ECLS). NB. ECLS is not usually appropriate for refractory vasoplegia.
• Torsades de pointes (due to sotalol)
  • Administer magnesium sulfate 10 mmol (0.05 mmol/kg in children) IV over 15 minutes.
  • Correct hypoxia, hypokalaemia and hypocalcaemia
  • If heart rate is <100 beats/minute commence an isoprenaline infusion IV at 1-10 microgram/min (0.05-2.0 microgram/kg/min in children) or overdrive pacing to maintain heart rate at 100-120 beats/minute.
• QRS widening and ventricular dysrhythmias (due to propanolol)
  • Suspect impending ventricular dysrhythmias if QRS >120 msec
  • Sodium bicarbonate 2 mmol/kg IV, can be repeated every 1-2 minutes to restore a perfusing rhythm and multiple doses maybe required; can titrate to effect by observing for QRS narrowing
  • Defibrillation can be attempted by may not be effective
  • Intubate and hyperventilate to target pH 7.5 to 7.55 to decrease sodium channel blockade
  • Lignocaine 1.5 mg/kg IV can be considered as a third line agent when the pH is >7.5.
  • Type Ia antidysrhythmic agents (e.g. procainamide) and amiodarone are contraindicated
• CNS effects
  • Drowsiness is commonly due to cardiovascular effects (e.g. hypotension) with most beta blockers and may respond to correction of hypotension.
  • However, propanolol has direct CNS effects requiring early intubation if progressive obtundation (e.g. GCS <12) or seizures, and hyperventilation to target pH 7.5 to 7.55

Supportive care and monitoring

• serial monitoring:
  • electrocardiography
  • cardiac output monitoring if severe toxicity (e.g. serial echocardiography, and/or continuous cardiac output monitors)
  • glucose and potassium
• FASTHUGS IN BED Please (as appropriate)

Investigations

• Screening
  • ECG (use QT nomogram if sotalol-induced QT prolongation; see QT interval)
  • paracetamol level
• Specific investigations (guided by clinical presentation)
  • Serial ECGs and cardiac monitoring for at least 4 hours
  • EUC
  • Echocardiography (especially if persistent hypotension)

Decontamination

• activated charcoal up to 2 hours post ingestion (4 hours if MR preparation)

Enhance elimination

• Nil

Antidotes

• Nil

Disposition

• Consult clinical toxicologist if evidence of significant toxicity or predicted by risk assessment
• Patients who are asymptomatic and have a normal ECG at 6 hours are medically cleared (12 hours if ingestion of MR formulation)
• Patients with clinical or ECG manifestations require admission to HDU or ICU.
• Refer for psychiatric assessment if potential deliberate self harm.

CONTROVERSIES

• Glucagon was previously considered an “antidote” for beta blocker toxicity, however a lack of evidence of effectiveness means it is no longer considered standard of care (see Glucagon as an Antidote).
• Intralipid is often considered a “last ditch measure” for lipid soluble toxicants, however evidence of effectiveness for beta blocker toxicity is lacking (see Intralipid and Lipid Rescue Therapy).

References and Links

LITFL

• CCC – Glucagon as an Antidote
• CCC – High-dose Insulin Euglycaemic Therapy
• CCC – Intralipid and Lipid Rescue Therapy
• ECG Library – Beta Blocker overdose
• Toxicology Library – Beta Blocker toxicity

Journals

• Boyd R, Ghosh A. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Glucagon for the treatment of symptomatic beta blocker overdose. Emerg Med J. 2003 May;20(3):266-7. PMC1726108.
• Lavonas EJ, Akpunonu PD, Arens AM, Babu KM, Cao D, Hoffman RS, Hoyte CO, Mazer-Amirshahi ME, Stolbach A, St-Onge M, Thompson TM, Wang GS, Hoover AV, Drennan IR; American Heart Association. 2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2023 Oct 17;148(16):e149-e184. doi: 10.1161/CIR.0000000000001161. Epub 2023 Sep 18. PMID: 37721023. [article]
• Lauterbach M. Clinical toxicology of beta-blocker overdose in adults. Basic Clin Pharmacol Toxicol. 2019 Aug;125(2):178-186. doi: 10.1111/bcpt.13231. Epub 2019 Apr 15. PMID: 30916882.
• Rotella JA, Greene SL, Koutsogiannis Z, Graudins A, Hung Leang Y, Kuan K, Baxter H, Bourke E, Wong A. Treatment for beta-blocker poisoning: a systematic review. Clin Toxicol (Phila). 2020 Oct;58(10):943-983. doi: 10.1080/15563650.2020.1752918. Epub 2020 Apr 20. PMID: 32310006.

FOAM and web resources

• Austin Health Toxicology Clinical Practice Guidelines – Beta Blocker Overdose