Propranolol Overdose

Propranolol overdose causes bradycardia, hypotension, cardiogenic shock, hypoglycaemia, seizures and coma. Its lipophilicity and membrane stabilising (sodium channel blocking) effect make it more dangerous than most beta blockers, with early central nervous system toxicity.

Propranolol is a leading cause of beta blocker deaths. Toxicity is likely above 1 g in adults (or 10 mg/kg), and seizures and coma can occur within 30 to 60 minutes of large ingestions. Children can be severely affected by small doses.

Risk factors for harm. Co-ingestion with calcium channel blockers or other cardiodepressants, modified release preparations, asthma, heart failure and large doses.

Course. Onset within 1 to 2 hours (up to 6 hours for modified release); effects last 24 to 48 hours.

Pathophysiology.

Beta-1 blockade reduces heart rate and contractility, and beta-2 blockade reduces glycogenolysis and bronchodilatation.

Sodium channel blockade widens the QRS and promotes ventricular arrhythmia and seizures, and brain penetration causes coma.

• Dizziness, weakness, bradycardia, hypotension and cold peripheries.
• Seizures, drowsiness, coma and respiratory arrest soon after ingestion.
• Wide QRS, ventricular tachycardia, atrioventricular block, cardiogenic shock and asystole.
• Hypoglycaemia, hyperkalaemia, bronchospasm and pulmonary oedema.

Red flags.

• Seizures or coma.
• QRS over 100 ms or ventricular arrhythmia.
• Shock or rapidly falling heart rate.

• History of dose, formulation and co-ingestants; paracetamol and salicylate levels.
• ECG on arrival and repeated (QRS, PR, QT); continuous monitoring.
• Glucose (repeated), potassium, calcium, lactate, renal function, venous gas and creatine kinase.
• Echocardiography when shock persists.

Differential diagnosis. Calcium channel blocker overdose, digoxin toxicity, tricyclic antidepressant overdose, clonidine toxicity, sepsis and cardiogenic shock.

• Resuscitation: airway, oxygen and cardiac monitoring; early intubation for seizures or coma.
• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 2 hours if the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness without a protected airway, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Glucagon for bradycardia and shock: 50 to 150 micrograms/kg (usual 5 to 10 mg) intravenously over 1 to 2 minutes, then 1 to 5 mg/hour infusion. Maximum 10 mg for a bolus. Monitor glucose, potassium and vomiting (protect the airway). Avoid in phaeochromocytoma and insulinoma.
• Atropine 0.5 mg intravenously, repeated every 3 to 5 minutes. Maximum 3 mg. Monitor heart rate and rhythm; avoid in angle closure glaucoma and urinary retention; response is usually poor.
• High dose insulin with euglycaemia: insulin 1 unit/kg intravenously as a bolus, then 1 unit/kg/hour infusion, titrated every 30 minutes up to 10 units/kg/hour; give glucose 25 g with the bolus and then glucose 0.5 g/kg/hour titrated to a glucose of 5 to 10 mmol/L. Maximum 10 units/kg/hour. Monitor glucose every 15 to 30 minutes, potassium and phosphate; avoid fluid overload.
• QRS over 100 ms: sodium bicarbonate 8.4% 1 to 2 mmol/kg (1 to 2 mL/kg) intravenously over several minutes, repeated until QRS is under 100 ms. Maximum serum pH 7.55 and sodium 150 mmol/L. Monitor ECG, pH, potassium and sodium.
• Seizures: lorazepam 0.1 mg/kg intravenously (maximum 4 mg for each dose) over 2 minutes, repeated once after 5 to 10 minutes if seizures continue. Maximum 8 mg in total. Monitor breathing, oxygen saturation, blood pressure and sedation. Use lower doses in older adults, respiratory disease and hepatic impairment; use only when needed in pregnancy.
• Vasopressors: noradrenaline 0.05 micrograms/kg/minute intravenously, titrated to a mean arterial pressure of 65 mmHg or higher (maximum 1 microgram/kg/minute; central line; monitor blood pressure, extravasation and arrhythmia).
• Hypoglycaemia: glucose 10% 2 mL/kg intravenously, repeated as needed, and infusion; monitor glucose hourly.
• Pacing, intravenous lipid emulsion (20% lipid emulsion 1.5 mL/kg bolus, then 0.25 mL/kg/minute for 30 to 60 minutes; maximum 10 mL/kg) and extracorporeal membrane oxygenation for refractory shock (specialist centre).
• Observe for at least 6 hours for immediate release products (24 hours for modified release or large ingestions), in a monitored setting.

Monitoring. Continuous ECG, arterial pressure, glucose hourly, potassium, lactate and neurological state.

Referral and escalation. Early poisons information centre and intensive care; cardiothoracic centre for extracorporeal support.

Special groups. Children: severe hypoglycaemia and seizures with small doses. Asthma: expect bronchospasm.