What are the presentation, ECG (electrocardiogram) findings, and treatment of flecainide toxicity?

Flecainide Toxicity: Presentation, ECG Findings, and Treatment

Clinical Presentation

Flecainide toxicity presents with cardiovascular collapse, altered mental status, and life-threatening arrhythmias, with mortality risk directly correlating to the degree of QRS widening on ECG. 1, 2

Key presenting features include:

• Cardiovascular manifestations: Hypotension, bradycardia, cardiac arrest, and cardiogenic shock are the predominant features 1, 3
• Neurological symptoms: Altered mental status, seizures, confusion, stupor, and depressed level of consciousness 1, 3
• Arrhythmias: New or worsened ventricular arrhythmias (7% incidence in therapeutic use), including ventricular tachycardia, ventricular fibrillation, and unresuscitatable cardiac arrest 1
• Congestive heart failure: New or worsened CHF occurs in 6.3% of patients, with higher rates (9.1%) in those with sustained VT 1
• Conduction abnormalities: Second-degree (0.5%) or third-degree (0.4%) AV block, sinus bradycardia, sinus pause, or sinus arrest (1.2% collectively) 1

Critical context: Flecainide toxicity can develop from acute overdose or accumulation in the setting of acute kidney injury, as renal impairment dramatically slows drug elimination 3. The therapeutic range is 0.2-1.0 μg/mL, with toxicity occurring above 1.5 μg/mL 3.

ECG Findings

The hallmark ECG finding in flecainide toxicity is progressive QRS widening, with QRS duration >200 ms predicting mortality and need for mechanical circulatory support. 2

ECG patterns stratified by QRS duration:

When QRS ≤200 ms 2:

• Right bundle branch block (RBBB) morphology is more common
• Visible P waves are typically present (p=0.03)
• Shorter QT and QTc intervals (p=0.02 and p=0.004 respectively)
• Heart rate may be out of proportion to hemodynamic instability

When QRS >200 ms 2:

• Left bundle branch block (LBBB) or RBBB morphology
• Loss of visible P waves
• Northwest axis deviation (p=0.01)
• Longer QT and QTc intervals
• Deaths reported ONLY in this group
• Death or requirement for mechanical circulatory support: 60% vs. 15.4% in QRS ≤200 ms group (p=0.04)

Critical diagnostic pitfall: Supraventricular tachycardia with flecainide toxicity can manifest as bizarre right or left bundle branch block, sometimes with northwest axis, and is easily mistaken for ventricular tachycardia, leading to inappropriate therapy 2.

Additional ECG features 1, 4:

• Bradycardia
• Prolonged QTc interval
• Wide complex tachycardia

Treatment Algorithm

Immediate treatment consists of sodium bicarbonate (1-2 mEq/kg IV bolus) to achieve arterial pH >7.45-7.55, with consideration of intravenous lipid emulsion (20%) for refractory cases, and extracorporeal membrane oxygenation (ECMO) for cardiovascular collapse. 5, 6, 4

Step 1: Initial Stabilization and Sodium Bicarbonate Therapy

Sodium bicarbonate is first-line therapy 5, 6:

• Administer 1-2 mEq/kg IV boluses until arterial pH >7.45
• Provide continuous infusion: 150 mEq NaHCO₃ per liter of D5W to maintain alkalosis
• In severe intoxication, increase pH to 7.50-7.55
• Mechanism: Sodium loading and alkalinization counteract sodium channel blockade

Step 2: Electrolyte Repletion

Aggressively correct electrolyte abnormalities 6:

• Hypokalemia must be corrected, as it exacerbates toxicity 3
• Monitor and maintain normal serum electrolytes

Step 3: Intravenous Lipid Emulsion Therapy

For refractory toxicity or cardiac arrest, administer 20% intravenous lipid emulsion 6, 4:

• Bolus dose followed by continuous infusion for 3 hours
• Has demonstrated successful conversion to normal sinus rhythm in case reports
• Can be used without concomitant extracorporeal support in some cases
• Mechanism: Lipid sink theory for lipophilic drug sequestration

Step 4: Hemodynamic Support

For persistent hypotension 5:

• Initial fluid resuscitation with normal saline boluses (10 mL/kg)
• If hypotension persists, epinephrine and norepinephrine are more effective than dopamine
• Avoid agitation-induced tachycardia, which may worsen outcomes 6

Step 5: Extracorporeal Support

Consider ECMO or cardiopulmonary bypass support for 5, 7:

• Cardiovascular collapse unresponsive to high-dose vasopressors
• Agonal rhythm with no effective blood pressure
• Persistently elevated flecainide levels causing refractory cardiac dysfunction
• Mechanism: Maintains hepatic perfusion to allow drug clearance (half-life during CBS: 6 hours) 7

Critical Contraindications in Treatment

DO NOT administer Class IA (quinidine, procainamide), Class IC (flecainide, propafenone), or Class III (amiodarone, sotalol) antiarrhythmics, as these will exacerbate cardiac toxicity 5.

Avoid inappropriate cardioversion or antiarrhythmic therapy for wide-complex rhythms that may represent supraventricular tachycardia with aberrancy rather than ventricular tachycardia 2.

Monitoring Requirements

Continuous cardiac monitoring and serial ECGs are essential 1:

• 80% of proarrhythmic events occur within 14 days of therapy initiation
• Monitor QRS duration as prognostic indicator
• Plasma level monitoring strongly recommended (therapeutic: 0.2-1.0 μg/mL; toxic: >1.5 μg/mL) 1, 3
• Flecainide levels may take days to result, so treatment should not be delayed pending laboratory confirmation 3

Special Considerations

In patients with renal impairment, flecainide elimination is markedly slower, requiring more aggressive and prolonged treatment 1. The combination of sepsis and acute kidney injury creates particularly high risk for flecainide accumulation 3.

Prognosis: Early detection and aggressive multimodal treatment are paramount given the high mortality associated with flecainide toxicity 4. QRS duration >200 ms is the strongest predictor of poor outcome 2.