What is the treatment for calcium channel blocker (CCB) overdose or severe adverse effects, specifically for reversing hypotension and cardiodepression?

From the Guidelines

The treatment for calcium channel blocker (CCB) overdose focuses on reversing hypotension and cardiodepression through a stepwise approach, with intravenous calcium administration and high-dose insulin euglycemia therapy being the primary treatments, as recommended by the most recent guidelines 1.

Initial Management

The initial management of CCB overdose includes gastrointestinal decontamination with activated charcoal if the patient presents within 1-2 hours of ingestion.

• Intravenous calcium administration is the first-line therapy, typically given as calcium gluconate 30 mL of 10% solution (3g) or calcium chloride 10 mL of 10% solution (1g), repeated every 15-20 minutes for 3-4 doses while monitoring calcium levels 1.
• High-dose insulin euglycemia therapy is often effective, starting with regular insulin at 1 unit/kg IV bolus followed by 0.5-1 unit/kg/hour infusion, alongside glucose supplementation to maintain normoglycemia 1.

Vasopressor Support

Vasopressors like norepinephrine (starting at 0.1-0.5 mcg/kg/min) or epinephrine may be needed for persistent hypotension, with the selection guided by the type of shock 1.

• Norepinephrine is recommended to increase blood pressure in vasoplegic shock or if myocardial function has not yet been assessed 1.
• Epinephrine is also recommended for a CCB-poisoned patient in shock to increase contractility and heart rate 1.

Refractory Cases

For refractory cases, lipid emulsion therapy (1.5 mL/kg bolus of 20% lipid emulsion followed by 0.25 mL/kg/min infusion) or glucagon (5-10 mg IV bolus followed by 1-5 mg/hour infusion) can be considered 1.

• Severe cases may require mechanical circulatory support with extracorporeal membrane oxygenation (ECMO) 1. These treatments work by overcoming calcium channel blockade through various mechanisms: direct calcium supplementation counteracts the blockade, high-dose insulin improves cardiac contractility and peripheral vascular resistance, while lipid emulsion creates a "lipid sink" to draw the lipophilic CCB away from tissues.

From the Research

Treatment for Calcium Channel Blocker Overdose

The treatment for calcium channel blocker (CCB) overdose or severe adverse effects, specifically for reversing hypotension and cardiodepression, involves several approaches:

• High-dose insulin euglycaemic therapy has become the mainstay of treatment in severe CCB OD, as reported in 2.
• Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest, although the evidence is of low quality 3.
• Calcium, dopamine, and norepinephrine improved hemodynamic parameters and survival without documented severe side effects, although the quality of evidence is very low 3.
• 4-Aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, but its use is limited by the risk of seizures 3.
• Lipid emulsion therapy was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but its effectiveness in humans is unclear 3.

Management of CCB Overdose

The management of CCB overdose requires prompt recognition and treatment, as severe CCB OD is often fatal:

• It is essential to recognize the signs and symptoms of CCB overdose, including bradycardia, peripheral vasodilation, and hypotension 4.
• Patients can develop both vasoplegic shock from peripheral vasodilation and cardiogenic shock, requiring careful management 4.
• The use of high-dose insulin, extracorporeal life support, and other treatments should be guided by the severity of the overdose and the patient's clinical condition 3, 2.

Comparison of Different CCBs

Different CCBs may have varying severity and treatment outcomes:

• Dihydropyridine overdoses, such as amlodipine, are increasingly common and may have a higher median defined daily dose ingested 5.
• Non-dihydropyridine CCBs, such as diltiazem and verapamil, may be associated with more severe toxicity, including dysrhythmias and hypotension 5.
• The treatment approach may vary depending on the specific CCB involved, with adrenaline and high-dose insulin more commonly used in diltiazem and verapamil overdoses 5.