What is the treatment for a cilnidipine (calcium channel blocker) overdose?

Treatment for Cilnidipine Overdose

Cilnidipine overdose should be managed identically to other calcium channel blocker (CCB) overdoses using high-dose insulin euglycemia therapy (HIET) as first-line treatment for refractory shock, combined with intravenous calcium administration. 1, 2

Initial Resuscitation and Stabilization

• Follow standard BLS and ACLS protocols for cardiac arrest or hemodynamic instability 1
• Establish continuous cardiac monitoring to detect bradycardia, AV blocks, and dysrhythmias 2
• Secure IV access immediately; central venous access is preferred if prolonged therapy is anticipated 1, 2
• Obtain baseline laboratory studies: serum glucose, potassium, ionized calcium, and renal function 2
• Consider gastric decontamination with activated charcoal (1-2 g/kg) if presentation is within 1-2 hours of ingestion and airway is protected 1

First-Line Pharmacologic Therapy

Intravenous Calcium (Initial Antidote)

Calcium should be administered immediately for catecholamine-refractory shock as it directly counteracts the calcium channel blockade 1, 2:

• Initial bolus: 0.3 mEq/kg IV over 5-10 minutes 1, 2
  • Use 10% calcium chloride: 0.2 mL/kg 1, 2
  • OR 10% calcium gluconate: 0.6 mL/kg 1, 2
• Continuous infusion: 0.3 mEq/kg per hour, titrated to hemodynamic response 1, 2
• Monitoring: Check serum ionized calcium levels; avoid severe hypercalcemia (>2× upper limit of normal) 1, 2
• Access: Sustained calcium infusions require central venous access to prevent tissue necrosis from extravasation 1

High-Dose Insulin Euglycemia Therapy (HIET)

HIET is the most effective therapy for restoring hemodynamic stability and improving survival in severe CCB toxicity (Class IIb, LOE B) 1, 2:

• Initial bolus: 1 U/kg regular insulin IV with simultaneous 0.5 g/kg dextrose bolus 1, 3, 2
• Continuous infusion:
  • Insulin: 0.5-1 U/kg/hour, titrated upward as needed for hemodynamic effect 1, 3, 2
  • Dextrose: 0.5 g/kg/hour, adjusted to maintain glucose 100-250 mg/dL 3, 2
• Glucose monitoring: Every 15 minutes initially during titration, then hourly once stable 3, 2
• Potassium monitoring: Every 1-2 hours; target 2.5-2.8 mEq/L (moderate hypokalemia is expected; aggressive repletion can cause asystole) 3, 2
• Mechanism: HIET improves myocardial inotropy and energy utilization in cardiogenic shock from CCB poisoning 3

Second-Line Therapies

Glucagon

• Dosing: 3-10 mg IV bolus over 3-5 minutes, followed by 3-5 mg/hour infusion 1
• Evidence: Insufficient and conflicting evidence for CCB overdose; may be considered if first-line therapies fail 1, 2
• Caveat: Glucagon commonly causes vomiting; protect airway before administration in patients with altered mental status 1

Vasopressors

• Norepinephrine: For vasoplegic shock to increase blood pressure 4
• Epinephrine: 2-10 mcg/min IV or 0.1-0.5 mcg/kg/min IV to increase contractility and heart rate 1, 4
• Dopamine: Less effective than epinephrine or norepinephrine; not preferred 3

Atropine

• Consider for symptomatic bradycardia or conduction disturbances, though efficacy is limited in CCB overdose 2

Advanced Rescue Therapies

Lipid Emulsion Therapy

• Administer IV lipid emulsion for refractory shock or periarrest states 2
• Consider for cardiac arrest from CCB toxicity 2

Extracorporeal Membrane Oxygenation (ECMO)

ECMO should be considered for shock refractory to all pharmacological interventions (Class 2b, LOE C-LD) 4, 3, 2:

• Indicated for refractory shock with significant cardiogenic component or cardiac arrest 2
• Retrospective studies show improved outcomes in drug toxicity-related cardiac arrest with ECMO 2
• Consensus supports ECMO for reversible causes like CCB toxicity 4, 2

Temporary Cardiac Pacing

• Use for unstable bradycardia or high-grade AV block WITHOUT significant myocardial dysfunction 2
• Pacing may be ineffective if severe myocardial depression is present 2

Mechanical Circulatory Support

• Intra-aortic balloon counterpulsation, ventricular assist devices, or other extracorporeal life support devices may be lifesaving in patients with treatment-refractory hypotension 1

Cardiac Arrest Management

• Follow standard ACLS algorithms with addition of IV calcium bolus 1, 2
• Consider IV lipid emulsion therapy 2
• Consider ECMO if available 2

Critical Monitoring Parameters

• Continuous cardiac telemetry: For rhythm and conduction abnormalities 2
• Blood pressure: Arterial line preferred for shock states 2
• Serum glucose: Every 15 minutes initially, then hourly once stable 3, 2
• Serum potassium: Every 1-2 hours during HIET 3, 2
• Ionized calcium levels: During calcium infusions 1, 2
• Observation period: Prolonged observation required for sustained-release formulations 1

Common Pitfalls to Avoid

• Do not under-dose insulin: The "high-dose" designation is critical; standard insulin doses will not achieve the desired hemodynamic effect 3
• Do not use lipid emulsion as first-line: Reserve for refractory cases or cardiac arrest 2
• Do not aggressively correct hypokalemia: Target moderate hypokalemia (2.5-2.8 mEq/L) to avoid asystole 3
• Do not rely on atropine or pacing alone: These are often ineffective without addressing the underlying myocardial depression 2
• Do not delay ECMO consultation: Early involvement of ECMO team is critical in refractory cases 4, 3, 2

Special Considerations for Cilnidipine

Cilnidipine is a fourth-generation CCB with dual L-type and N-type calcium channel blocking properties 5, 6, 7. While no specific overdose data exists for cilnidipine, its N-type channel blockade may theoretically cause additional sympathetic inhibition beyond typical CCBs 6, 7. However, treatment should follow the same CCB overdose protocols outlined above, as the fundamental pathophysiology of calcium channel blockade remains the same 1, 2.

Consultation

Prompt consultation with a medical toxicologist or poison control center (1-800-222-1222) is strongly recommended for all CCB overdoses to guide therapy and ensure access to advanced interventions 1.