Question

A 46-year-old man is brought to the emergency department after intentionally ingesting a large quantity of his antihypertensive medication. He is drowsy and complains of dizziness.

On examination:

• Heart rate: 38 beats/min
• Blood pressure: 76/42 mmHg
• Respiratory rate: 18 breaths/min
• Oxygen saturation: 97% on room air

ECG shows marked sinus bradycardia with first-degree heart block. His capillary glucose is 3.1 mmol/L. The medication list includes propranolol.

Despite intravenous fluids and atropine, he remains profoundly hypotensive and bradycardic.

Which of the following is the most appropriate specific antidotal treatment?

A. Intravenous calcium gluconate
B. Intravenous sodium bicarbonate
C. Intravenous glucagon
D. Intravenous N-acetylcysteine
E. Intravenous lipid emulsion

Answer

C. Intravenous glucagon

Explanation

This patient has severe beta-blocker poisoning, suggested by the combination of profound bradycardia, hypotension, conduction disturbance and hypoglycaemia following propranolol ingestion.

The classic cardiovascular manifestations of beta-blocker overdose are bradycardia and hypotension. Increasing toxicity may produce AV block, cardiogenic shock and cardiovascular collapse.

Propranolol is particularly important because it is highly lipophilic and also has membrane-stabilising, sodium-channel-blocking activity. Consequently, propranolol overdose can cause CNS depression, seizures and QRS widening in addition to the usual features of beta-blockade. Sodium bicarbonate should therefore be considered when significant QRS widening due to propranolol occurs, but it is not the main specific antidote to beta-blockade.

Glucagon is a traditional specific treatment for severe beta-blocker toxicity. It binds to glucagon receptors on cardiac myocytes and activates adenylyl cyclase independently of beta-adrenergic receptors. This increases intracellular cyclic AMP, improving heart rate and myocardial contractility despite beta-receptor blockade.

In severe poisoning, glucagon is given intravenously as a bolus, commonly approximately 2–10 mg depending on local toxicology guidance, followed by an infusion if there is a clinical response. Nausea and vomiting are common adverse effects, so airway protection should be considered in patients with impaired consciousness.

Atropine may be attempted for symptomatic bradycardia but is frequently ineffective in severe beta-blocker poisoning. Intravenous fluids and vasopressors may be required to maintain perfusion.

High-dose insulin euglycaemia therapy is extremely important in severe or refractory beta-blocker poisoning, particularly when myocardial dysfunction and shock persist. Insulin improves myocardial carbohydrate utilisation and has positive inotropic effects. Because it can cause profound hypoglycaemia and hypokalaemia, frequent glucose and potassium monitoring is essential, with intravenous glucose supplementation.

Temporary cardiac pacing may be required in refractory severe bradycardia or high-grade heart block, although electrical capture does not always result in adequate haemodynamic improvement.

Beta-blockers may also mask the adrenergic manifestations of hypoglycaemia, particularly tachycardia and tremor, so glucose should be checked repeatedly. Non-selective beta-blockers such as propranolol may additionally precipitate bronchospasm.

A useful examination distinction is that calcium-channel blocker overdose often causes hyperglycaemia, whereas beta-blocker overdose may be associated with hypoglycaemia.

Summary for quick exam revision

Beta-blocker overdose classically causes bradycardia and hypotension and may progress to AV block, cardiogenic shock and cardiovascular collapse. Severe toxicity should be suspected when profound bradycardia persists despite initial fluids and atropine. Glucagon is the classic specific antidotal treatment because it activates cardiac adenylyl cyclase through glucagon receptors independently of blocked beta-receptors, thereby increasing cyclic AMP, heart rate and contractility. It is generally given as an intravenous bolus followed by an infusion if effective. Nausea and vomiting are important adverse effects of glucagon, particularly in patients with reduced consciousness. Propranolol deserves special attention because it is highly lipophilic, crosses the blood-brain barrier and can cause seizures and CNS depression. Propranolol also has membrane-stabilising sodium-channel-blocking activity and can therefore produce QRS widening. Significant QRS widening in propranolol poisoning may require intravenous sodium bicarbonate. Atropine can be tried for symptomatic bradycardia but is often insufficient in major poisoning. High-dose insulin euglycaemia therapy is a key treatment for persistent shock or myocardial dysfunction and requires close glucose and potassium monitoring. Vasopressors may also be required when hypotension remains severe. Temporary pacing can be considered for refractory bradycardia or high-grade heart block, although haemodynamic response may be limited. Blood glucose should be checked repeatedly because beta-blocker toxicity may cause hypoglycaemia and beta-blockade can mask its adrenergic warning symptoms. Non-selective beta-blockers can also cause bronchospasm. For rapid exam recognition, think beta-blocker overdose when bradycardia + hypotension ± hypoglycaemia are present, remember propranolol for seizures and wide QRS, and remember glucagon plus high-dose insulin therapy for severe cardiovascular toxicity.