High-Dose Insulin in Calcium Channel Blocker Toxicity

A 34-year-old, 70 kg female presents to the emergency department after ingestion of 45 mg of amlodipine. The time of ingestion is unknown and on presentation, the patient is awake, alert, and oriented with normal vital signs. Two hours after presentation, the patient’s heart rate slows to  42 bpm, and systolic blood pressure is found to be 89 mmHg. The patient does not respond to calcium gluconate or fluid resuscitation. What’s the next option?   

Introduction

In general, CCB overdose patients present with the following clinical manifestations:

• Bradycardia
  • In mild overdose dihydropyridines (amlodipine, nifedipine) can result in reflex tachycardia 
• Hypotension
• Decreased systemic vascular resistance
• Cardiogenic shock 
• Hyperglycemia

Mechanism of Toxicity 

• Under normal conditions, the calcium concentration gradient allows for cell function and contraction and relaxation of muscle cells throughout the body. 
• Classic calcium channel blocker toxicity results in depressed myocardial contractions and peripheral vasodilation (aka hypotension and bradycardia). 
• While calcium channel blocker overdose and beta-blocker overdose have similar presentations, unique to calcium channel blocker overdose is drug-induced hyperglycemia:
  • In drug-induced shock, the body breaks down carbohydrates instead of free fatty acids as an energy source, ultimately increasing the glucose demand of the heart.

High Dose Insulin’s Role

1. Supports metabolic demand by increasing myocardial contractility and tissue perfusion.
2. Has positive inotropic effects at high doses. 

Insulin Goal

Increase cardiac output, improve mental status, vital signs (heart rate, blood pressure), reverse metabolic abnormalities (serum lactate, bicarbonate pH, urine output).

Insulin Dose: 

• In the setting of toxicity, insulin is weight-based 
• 1 unit/kg bolus followed by 2-10 units/kg/hr 
  • Doses up to 22 units/kg/hr have been used. A maximum dose is not established.3

Insulin Formulation

• Use concentrated insulin 10 units/mL or 16 units/mL. 
• The standard concentration of insulin is 1 unit/mL which can quickly fluid overload the patient. 
  • Ex. 80 kg patient dosed at 10 units/kg/hr
    • 1 unit/mL concentration = 800 mL/hr 
    • 10 unit/mL concentration = 80 mL/hr
    • 16 unit/mL concentration =  50 mL/hr 

Concurrent Dextrose

Ensuring glucose is 100-150 mg/dL or greater is reasonable.

• Consider running a continuous dextrose infusion- 0.5 grams/kg/hr concurrently with insulin
• Dextrose 10% infusion can be started however it is recommended to utilize D25 or D50 infusion through central venous access to decrease additional fluid burden. 
• If the patient becomes hypoglycemic, don’t try to decrease the insulin dose, rather increase the dextrose requirement 

Insulin Risks

Hypoglycemia

1. Point of care glucose every 30 minutes until stable than ever 1-2 hours

Hypokalemia

Potassium- insulin shifts the potassium to the intracellular space thereby reducing serum potassium levels. 

1. Check baseline potassium, and then every 6 hours. Hospital protocols will vary in goal potassium level, however ensuring potassium >3.5 meq/L is reasonable.  

Weaning Insulin off

• While not clearly described in the literature, a reasonable approach to discontinuing HIE is to decrease insulin by 1 unit/kg/hr every 1 hour or 2 units/kg/hr every 2 hours (depends on the nurse’s availability) until off.  
• Dextrose supplementation should continue for the first 24 hours after insulin discontinuation
• Potassium concentrations should also be assessed after insulin discontinuation