Calcium Channel Blocker Overdose

Calcium channel blockers (verapamil, diltiazem, nifedipine, amlodipine, felodipine) cause vasodilatory and cardiogenic shock. Verapamil and diltiazem are non-dihydropyridines that act on the sinoatrial node, atrioventricular node and myocardium, causing bradycardia, block and reduced contractility. Dihydropyridines (amlodipine, nifedipine) act mainly on vascular smooth muscle, so they cause vasodilation and reflex tachycardia, but in large overdose they also lose selectivity and cause bradycardia and myocardial depression.

Verapamil is the most lethal drug in the group, and a single sustained-release tablet can kill a toddler. Ingestion of over 10 mg/kg of verapamil or over 1 mg/kg of amlodipine in a child is dangerous. Amlodipine has a half-life of 30 to 50 hours, so shock is prolonged. Sustained-release products can delay onset for up to 12 to 24 hours.

Calcium channel blockers also block insulin release from beta cells, producing hyperglycemia, which is a marker of severity. Complications: refractory shock, noncardiogenic pulmonary edema (especially with amlodipine and aggressive fluids), mesenteric ischemia, lactic acidosis and cardiac arrest.

• Nausea, vomiting, dizziness, lethargy and confusion
• Bradycardia, atrioventricular block (any degree), hypotension, cool or warm peripheries
• Dihydropyridines: profound vasodilation and flushing with reflex tachycardia early
• Hyperglycemia, metabolic acidosis, hypokalemia, hypocalcemia
• Pulmonary edema, seizures and coma
• Red flags: systolic blood pressure under 90 mmHg, heart rate under 50 beats a minute, high-grade block, hyperglycemia over 11 mmol/L and a sustained-release ingestion

1. 12-lead ECG and continuous monitoring (at least 6 hours, and 24 hours for sustained-release preparations).
2. Glucose, lactate, blood gases, potassium, calcium (ionized), magnesium, creatinine, liver tests.
3. Bedside echocardiography: contractility and volume status.
4. Paracetamol and salicylate levels, and a coingestant screen, particularly beta blockers.
5. Chest radiograph for pulmonary edema.

Differentials: beta blocker overdose, clonidine toxicity, digoxin toxicity, organophosphate poisoning, sepsis, anaphylaxis, myocardial infarction.

1. Resuscitation: secure the airway if needed, IV crystalloid 10 mL/kg only cautiously (to avoid pulmonary edema), and invasive blood pressure monitoring.
2. Decontamination: activated charcoal 50 g orally (children 1 g/kg, maximum 50 g) within 1 to 2 hours. Whole bowel irrigation (polyethylene glycol 2 L/h orally or by tube, children 25 mL/kg/h) for sustained-release ingestions in patients with a protected airway.
3. Calcium: calcium chloride 10% 10 to 20 mL IV (children 0.2 mL/kg) over 5 to 10 minutes, repeated every 10 to 20 minutes up to 3 to 4 doses, then infusion 0.2 to 0.4 mL/kg/h (up to 20 to 40 mL/h in adults) through a central line. Calcium gluconate 10% 30 to 60 mL (children 0.6 mL/kg) is an alternative by peripheral vein. Target ionized calcium of 1.5 to 2 mmol/L and monitor for hypercalcemia.
4. High-dose insulin euglycemia therapy (a mainstay for shock and bradycardia):
   • Regular insulin 1 unit/kg IV bolus with 25 g dextrose (if glucose is under 14 mmol/L).
   • Infusion 1 unit/kg/h, increased every 30 minutes by 1 unit/kg/h to a maximum of 10 units/kg/h until hemodynamic improvement.
   • Dextrose 10% or 20% at 0.5 g/kg/h titrated to glucose of 6 to 10 mmol/L, monitored every 30 minutes initially.
   • Keep potassium at 3.0 to 3.5 mmol/L and monitor magnesium and phosphate.
5. Vasopressors and inotropes: norepinephrine 0.05 to 1 microgram/kg/min or epinephrine 0.05 to 1 microgram/kg/min, titrated to mean arterial pressure over 65 mmHg. Vasopressin 0.03 to 0.04 units/min for vasoplegia.
6. Atropine 0.5 to 1 mg IV (children 20 micrograms/kg) for bradycardia. It is often ineffective.
7. Lipid emulsion 20%: 1.5 mL/kg IV bolus then 0.25 mL/kg/min for 30 to 60 minutes (maximum 12 mL/kg) for refractory shock, particularly with verapamil and diltiazem.
8. Refractory vasoplegia: methylene blue 1 to 2 mg/kg IV over 20 minutes.
9. Refractory shock: transvenous pacing and venoarterial extracorporeal membrane oxygenation, started early.
10. Pulmonary edema: oxygen and positive pressure ventilation, and avoid further fluids. Dialysis is not useful.

Observation for at least 6 hours for immediate-release and 24 hours for sustained-release products (and 24 to 48 hours for amlodipine in children), with psychiatric assessment before discharge.