What are the treatment steps for an Amlodipine (calcium channel blocker) overdose?

Management of Amlodipine Overdose

For amlodipine overdose with hemodynamic instability, immediately initiate high-dose insulin euglycemia therapy (HIET) and vasopressors (particularly norepinephrine), with calcium administration as first-line therapy, and prepare for VA-ECMO if shock remains refractory to maximal pharmacologic support. 1, 2

Initial Stabilization and Monitoring

• Establish continuous cardiac monitoring to detect bradycardia, conduction abnormalities, and dysrhythmias that commonly occur with calcium channel blocker toxicity 3, 2
• Secure IV access immediately, preferably central venous access if prolonged intensive therapy is anticipated 3
• Obtain baseline labs: serum glucose, potassium, ionized calcium, and renal function 3
• Initiate gastric decontamination with activated charcoal (1-2 g/kg) only if presentation is within 1-2 hours of ingestion and airway is protected 3
• Place arterial line for continuous blood pressure monitoring in shock states 3
• Contact poison control center (1-800-222-1222) or medical toxicologist immediately for all amlodipine overdoses to guide therapy 3

Critical pitfall: Amlodipine causes prolonged hypotension lasting several days due to its long elimination half-life (approximately 55 hours), requiring extended monitoring even if initially stable 2, 4, 5

First-Line Pharmacologic Therapy

High-Dose Insulin Euglycemia Therapy (HIET)

• HIET is the most effective therapy for severe calcium channel blocker toxicity, improving cardiac contractility with lower rates of vasoconstrictive complications than vasopressor-only therapy 1, 2
• Administer 1 U/kg regular insulin IV bolus with simultaneous 0.5 g/kg dextrose bolus 3, 2
• Follow with continuous infusion of 0.5-1 U/kg/hour insulin and 0.5 g/kg/hour dextrose 3, 2
• Monitor serum glucose and potassium every 15 minutes initially, then hourly once stable 3
• Protocolized care reduces hypoglycemia risk; hypokalemia and volume overload are additional concerns requiring vigilant monitoring 1

Calcium Administration

• Calcium is recommended as first-line treatment for catecholamine-refractory shock, directly counteracting calcium channel blockade 1, 3, 2
• High doses targeting ionized calcium concentrations up to twice normal appear more effective than lower doses 1
• Monitor ionized calcium levels during infusions 3
• Most patients require additional treatments beyond calcium alone 1

Vasopressor Therapy

• Norepinephrine is the preferred vasopressor, with doses up to 100 μg/min in adults demonstrating excellent survival rates and low ischemic complications 1, 2
• One large retrospective series showed excellent outcomes with primary vasopressor use 1

Second-Line and Adjunctive Therapies

Atropine

• Commonly used first-line for bradycardia, but treatment failures are reported 1
• May be reasonable for initial bradycardia management while preparing definitive therapies 1

Glucagon

• Variable response rates with common vomiting and rapid tachyphylaxis 1
• Consider as adjunctive therapy only, not as primary treatment 1

Methylene Blue

• May be effective for refractory vasodilatory shock specifically from amlodipine overdose (as a nitric oxide synthase inhibitor) 1
• Responses are mixed and effects may be transient 1
• Consider when vasodilatory shock persists despite other interventions 6

Electrical Pacing

• Results are mixed; may be reasonable for hemodynamically significant bradydysrhythmias 1
• Not always effective, particularly with complete AV nodal blockade or vasodilatory shock 1

Rescue Therapy for Refractory Shock

VA-ECMO

• VA-ECMO may be lifesaving for persistent cardiogenic shock refractory to maximal supportive care, with reported survival rates as high as 77% 1, 2
• Should be considered early when shock remains refractory to pharmacological interventions 3, 2
• Case reports demonstrate successful outcomes even after cardiac arrest 1, 6

Plasmapheresis and Hemodialysis

• Hemodialysis is not likely to be beneficial as amlodipine is highly protein bound 7
• Continuous veno-venous hemodialysis (CVVHD) has been reported in combination therapy with some success 8
• Plasmapheresis has been attempted in refractory cases but evidence is extremely limited 6

Therapies NOT Recommended

Intravenous Lipid Emulsion (ILE)

• The American Heart Association advises against routine use of ILE for calcium channel blocker poisoning 1, 2
• A large retrospective study found no benefit from ILE therapy 1
• ILE may increase absorption of lipophilic drugs from the gastrointestinal tract, potentially worsening oral overdose 1, 2

Critical Monitoring and Supportive Care

• Fluid administration must be judicious; volume overload and pulmonary edema can develop rapidly even with relatively low-volume replacement 4, 5
• One case developed pulmonary edema after only 1.5 L of normal saline 4
• Another case had 7 L volume overload in first 24 hours requiring CPAP and diuretics 5
• Elevation of extremities may help with hypotension 7
• Extended clinical monitoring is essential due to prolonged hemodynamic effects lasting days 7, 4

Common Pitfalls to Avoid

• Do not delay HIET while waiting for calcium or vasopressors to work; early aggressive multi-modal therapy improves outcomes 8, 9
• Do not underestimate the duration of toxicity; amlodipine effects can persist for days requiring prolonged ICU care 2, 4, 5
• Do not give excessive fluids; amlodipine overdose predisposes to pulmonary edema 4, 5
• Do not use ILE routinely; it may worsen outcomes 1, 2
• Do not delay ECMO consultation if shock persists despite maximal therapy; early ECMO improves survival 1, 2