Verapamil Overdose

Verapamil overdose causes bradycardia, atrioventricular block, cardiogenic shock and hyperglycaemia. It is the most lethal calcium channel blocker in overdose because of combined myocardial depression and vasodilatation.

Verapamil accounts for a large share of calcium channel blocker deaths. Toxicity is likely at over 5 mg/kg or over 1 g in adults, and a single tablet of modified release verapamil can be fatal in a toddler.

Risk factors for harm. Modified release preparations, co-ingestion with beta blockers or digoxin, heart disease, hepatic impairment and children.

Course. Onset can be delayed up to 6 to 12 hours for modified release preparations, with toxicity lasting 24 to 72 hours.

Pathophysiology.

Blockade of L-type calcium channels in the sinoatrial and atrioventricular nodes slows conduction, and in myocardium reduces contractility, while vasodilatation reduces afterload.

Impaired insulin release causes hyperglycaemia, and cells switch away from free fatty acid metabolism.

• Dizziness, nausea, vomiting, confusion and drowsiness.
• Bradycardia, first to third degree heart block, junctional rhythm and asystole.
• Hypotension, cardiogenic shock and pulmonary oedema.
• Hyperglycaemia, metabolic acidosis, ileus and seizures.

Red flags.

• Heart rate under 50 beats/minute or complete heart block.
• Hypotension, shock or rising lactate.
• Any ingestion in a child.

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

Differential diagnosis. Diltiazem or beta blocker overdose, digoxin toxicity, clonidine toxicity, hyperkalaemia, myocardial infarction and sepsis.

• Resuscitation: airway, oxygen and cardiac monitoring; early intravenous access and central line.
• 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, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Whole bowel irrigation for modified release ingestions with a protected airway: polyethylene glycol electrolyte solution 1 to 2 litres/hour orally or via nasogastric tube (children 25 mL/kg/hour) until the rectal effluent is clear. Monitor for vomiting, aspiration and distension. Avoid in ileus, obstruction, shock and an unprotected airway.
• 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 often poor.
• Calcium chloride 10% 10 mL (6.8 mmol) intravenously over 5 to 10 minutes through a central line (or calcium gluconate 10% 30 mL peripherally), repeated every 10 to 20 minutes up to 3 doses, then infusion of calcium gluconate 10% 0.2 to 0.4 mL/kg/hour. Maximum 3 bolus doses in the first hour. Monitor ionised calcium, ECG and extravasation. Avoid in digoxin toxicity; use caution in renal impairment.
• 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.
• 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.
• 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).
• Intravenous lipid emulsion for peri-arrest or refractory shock: 20% lipid emulsion 1.5 mL/kg bolus, then 0.25 mL/kg/minute for 30 to 60 minutes. Maximum 10 mL/kg in total. Monitor pancreatitis and fluid load.
• Pacing for refractory bradycardia (often poorly responsive), and extracorporeal membrane oxygenation for refractory shock or arrest (specialist centre).
• Observe in a monitored setting for at least 24 hours for modified release or large ingestions; 6 hours for small ingestions of immediate release products with a normal ECG.

Monitoring. Continuous ECG and arterial pressure; glucose, potassium, calcium and lactate every 1 to 2 hours during insulin therapy.

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

Special groups. Children: one tablet can be fatal. Pregnancy: the same treatment applies, with obstetric input.