What is the role of Mexilitine in treating Ventricular Tachycardia (VTach) storm?

Mexiletine in the Treatment of Ventricular Tachycardia Storm

Mexiletine is recommended as a second or third-line agent for ventricular tachycardia storm, particularly when used in combination with Class Ia antiarrhythmic drugs or amiodarone after first-line therapies have failed. 1, 2

Mechanism and Indications

Mexiletine is a Class 1B antiarrhythmic agent with electrophysiologic properties similar to lidocaine but with the advantage of oral administration. It works by:

• Inhibiting inward sodium current, reducing the rate of rise of the action potential (Phase 0)
• Decreasing the effective refractory period in Purkinje fibers 2

The FDA has approved mexiletine for:

• Treatment of documented life-threatening ventricular arrhythmias, including sustained ventricular tachycardia
• Not recommended for lesser arrhythmias or asymptomatic ventricular premature contractions 2

Place in VT Storm Management Algorithm

1. First-line therapies:

   • Beta-blockers (IV metoprolol 5 mg over 1-2 minutes, repeated as needed to maximum 15 mg)
   • Amiodarone (300 mg IV bolus, followed by 1 mg/min infusion for 6 hours, then 0.5 mg/min)
   • Correction of underlying causes (ischemia, electrolyte abnormalities) 3, 1

2. Second-line options:

   • Lidocaine for ischemia-related VT (1-1.5 mg/kg IV bolus, followed by 2-4 mg/min infusion)
   • Procainamide (20-50 mg/min until arrhythmia suppressed or maximum dose reached) 1

3. Role of mexiletine:

   • Add-on therapy when first-line agents fail
   • Particularly useful in combination with Class Ia drugs (synergistic effect)
   • Option for patients who cannot tolerate amiodarone
   • Specific indication for LQT3-related torsades de pointes 3, 4

Dosing and Administration

• Standard dose: 400-600 mg/day divided into three doses (most common effective dose)
• May start at lower doses (200 mg three times daily) and titrate based on response
• Initiation should occur in a hospital setting with continuous cardiac monitoring 1, 2

Efficacy in VT Storm

Mexiletine has demonstrated efficacy in several scenarios:

• As monotherapy, suppresses electrically-inducible VT in approximately 23% of patients 4
• More effective when combined with Class Ia drugs, with 29% efficacy rate 4
• More effective for non-sustained VT or ventricular fibrillation than for sustained VT 4
• Significantly reduces electrical storm events, VT/VF episodes, and ICD interventions in patients with recurrent ventricular arrhythmias 5

Special Considerations

1. Specific VT subtypes:

   • May be particularly useful in LQT3-related torsades de pointes 3
   • Less effective for sustained monomorphic VT compared to other forms 4

2. Combination therapy:

   • Often more effective when combined with Class Ia drugs or amiodarone
   • Consider as part of multi-drug regimen for refractory cases 4, 5

3. Monitoring requirements:

   • Continuous cardiac monitoring during initiation
   • Regular assessment of liver function (90% hepatic metabolism)
   • ECG monitoring (though minimal effect on QRS and QT intervals) 1, 2

Adverse Effects and Limitations

• Gastrointestinal and neurologic side effects are common (occurring in up to 60% of patients)
• Discontinuation rates due to adverse effects range from 9-40% in various studies
• Side effects appear to be dose-related
• Limited efficacy as monotherapy (23% success rate) 6, 7

Clinical Pearls

• Mexiletine does not significantly alter QT intervals, making it safer in patients with prolonged QT
• Unlike many other antiarrhythmics, it has minimal negative inotropic effects
• Consider as an alternative when amiodarone is contraindicated or poorly tolerated
• Most effective when used as part of a combination therapy approach 1, 2, 5

Long-term Management

For patients who respond to mexiletine during acute management:

• Long-term therapy can be effective with a 5.5% per year arrhythmia recurrence rate
• Approximately 57% of patients can continue therapy long-term
• Consider catheter ablation for recurrent episodes despite medical therapy 8, 1

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