Diltiazem Overdose

Diltiazem overdose causes bradycardia, atrioventricular block and hypotension, similar to verapamil but with a slightly lower tendency for severe cardiogenic shock. Modified release preparations cause delayed and prolonged toxicity.

Diltiazem is a commonly prescribed non-dihydropyridine calcium channel blocker. Toxicity is likely over 5 mg/kg or 1.2 g in adults, and severe toxicity above 3 g. Children can be affected by one or two tablets.

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

Course. Onset can be delayed up to 12 hours with modified release products, and toxicity may last 24 to 72 hours.

Pathophysiology.

Blockade of L-type calcium channels in the sinoatrial and atrioventricular nodes slows conduction, with moderate myocardial and vascular smooth muscle effects.

Diltiazem inhibits CYP3A4, so it raises levels of co-ingested drugs.

• Dizziness, nausea, vomiting, flushing and drowsiness.
• Sinus bradycardia, atrioventricular block (first, second or third degree), junctional rhythm and asystole.
• Hypotension, cardiogenic shock, pulmonary oedema and hyperglycaemia.
• Metabolic acidosis, ileus and acute kidney injury in severe cases.

Red flags.

• Heart rate under 50 beats/minute or high grade heart block.
• Hypotension or rising lactate.
• Co-ingestion of beta blockers or digoxin.

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

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

• Resuscitation: airway, oxygen, cardiac monitoring and intravenous access; central line for infusions.
• 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.
• 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: 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. 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).
• Transvenous pacing for symptomatic bradycardia or block; extracorporeal membrane oxygenation for refractory shock (specialist centre).
• Observe in a monitored setting for at least 24 hours for modified release or large ingestions; 6 hours for small immediate release ingestions 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. Poisons information centre and intensive care for all significant ingestions.

Special groups. Children: admit with any modified release ingestion. Pregnancy: the same treatment applies, with obstetric input.