Calcium Channel Blockers

Background
CCB’s are divided into two categories: dihydropyridines (amlodipine, nifedipine) and non-dihydropyridines (diltiazem, verapamil). Dihydropyridines affect more peripheral calcium channels and non-dihydropyridines affect more cardiac calcium channels. In overdose, the selectivity for the dihydropyridines is lost. In CCB poisoning, the heart changes its energy source from free fatty acids to carbohydrates; however, insulin release is a calcium mediated process and inhibition of calcium channels in the pancreas prevents insulin release leading to hyperglycemia. It is thought that high-dose insulin therapy helps to increase contractility through increasing the cardiac utilization of glucose. It is not likely to help with vasodilation or bradycardia.

 

Evaluation

  • Physical Exam: Markedly preserved mental status until patient is about to code; dihydropyridines: reflex tachycardia with bounding pulses (in some cases)
  • Labs: Hyperglycemia (glucose >330 is poor prognostic sign)
  • ECG: Can show high-degree heart block (3rd degree and complete AV dissociation)

 

 

Management

  • IVF, vasopressors, calcium, and high-dose insulin/euglycemic therapy (HIE)
  • For HIE, the dosing is 0.5-1 unit/kg bolus followed by 0.5-1 unit/kg/hour infusion titrated up to 10 units/kg/hour to treat hypotension. Dextrose should be given to maintain euglycemia. This should be titrated as a pressor with the awareness that changes in blood pressure can take about 20 minutes to take effect.
  • Intralipid should be used in code/refractory hypotensive situations for lipophilic CCB’s (verapamil, amlodipine, diltiazem). VA-ECMO should be considered as a last resort after medical therapy has failed.

 

Quick dosing reference: if hypotensive and bradycardic:

  • High-dose insulin 0.5-1 unit/kg bolus followed by 0.5-1 unit/kg/hour infusion titrated to up to 10 units/kg/ hour. Call Toxicology immediately if exceeding 3 units/kg/hour.
  • Vasopressors: Norepinephrine (0.01 to 3 mcg/kg/min – adjust rate per ICU protocol) or epinephrine (0.05 to 2 mcg/kg/min – adjust rate per ICU protocol)
  • Calcium: 3g calcium gluconate
  • Intralipid infusions for verapamil, amlodipine, diltiazem (1 liter over 1 hour) for refractory hypotension or if patient codes.
    • Other dosing is 1.5 cc/kg bolus followed by 0.25 cc/kg/min over 60 min but for a 70 kg adult, this equates to 1 liter over 1 hour.