Antidysrhythmic Toxicity Treatment & Management

An advanced life support (ALS) unit is recommended for transport and establishment of ABCs.

Airway, breathing, circulatory support, IV access, and ECG monitoring are of paramount importance. Torsade de pointes is the most common proarrhythmia encountered. (See Torsade de pointes treatment following the individual discussion of the drugs.)

Treatment based on grouping is as follows (for more details on each respective agent, refer to each individual section):

• GI decontamination - Disopyramide, quinidine, flecainide, propafenone, ajmaline/cibenzoline/detajmium, amiodarone, and N -acetyl procainamide
• Hemodialysis - Disopyramide, procainamide, mexiletine/tocainide, and bretylium (limited experience)
• Pacemaker or intra-aortic balloon pump (IABP) - Procainamide, quinidine, propafenone, ajmaline/cibenzoline/detajmium, and amiodarone
• Pressors - Quinidine, amiodarone, and propafenone
• Seizure control - Quinidine, lidocaine, flecainide, and propafenone

All dysrhythmias resulting from sodium channel poisons may respond to sodium bicarbonate or cautious hypertonic saline therapy.

Disopyramide - Class IA

GI decontamination is warranted to decrease GI disopyramide absorption because of its anticholinergic effects. Hemodialysis is effective in decreasing the serum half-life and may be useful when supportive care is not effective. Unfortunately, no significant clinical experience is available to guide therapy. Calcium chloride doses of 0.5 g every 5 minutes (up to maximum of 3 g) in combination with ACLS therapy may be required.

Procainamide - Class IA

Implement supportive. GI decontamination and activated charcoal are indicated following an oral overdose. If renal failure is present, consider hemodialysis even though its role has not yet been defined. Avoid quinidine and disopyramide. Consider early pacemaker with increasing atrioventricular block. VF/VT in the setting of Brugada syndrome is best managed with isoproterenol as opposed to amiodarone.

Quinidine - Class IA

After IV, oxygen, and cardiac monitoring are initiated, seizures may be responsive to diazepam or any other benzodiazepine of choice; check electrolyte levels, especially calcium, and glucose if seizures are not responsive. GI lavage and/or activated charcoal, with repeated doses, may be indicated. Treat hypotension with fluids and then pressors. Isoproterenol and norepinephrine have been used successfully. Use IABP as a last resort. Use class IB agents for treating dysrhythmias; avoid class IA drugs. Correct electrolyte imbalances (eg, potassium, calcium) and glucose. Dialysis is not helpful. Experience with charcoal hemoperfusion is limited. Glucagon has been proven useful in animal models but such data are lacking in humans.

Lidocaine - Class IB

Supportive measures are sufficient because of the short half-life (2.7-3.8 h). Consider extracorporeal pump for massive overdose, which have been useful in reducing mortality.

Adequate ventilation and perfusion is imperative because hypoxia and hypercarbia increases penetration of basic drug lidocaine into brain. Use diazepam for seizures. Avoid phenytoin because of its synergistic cardiac effects.

Mexiletine and tocainide - Class IB, lidocaine analogs

No antidotes are available for either drug. GI decontamination based on emesis is contraindicated because of very rapid development of seizures. Theoretically, hemodialysis could decrease the serum level of these agents and alkalinization of urine would increase serum level.

Encainide - Class IC

Transport as quickly as possible to ED. Do not be fooled by the "they-look-good" syndrome because individuals with encainide toxicity can decompensate quickly. GI decontamination is relatively contraindicated because encainide is quickly absorbed. Treating overdose with hypertonic sodium bicarbonate and hypertonic saline reportedly has been successful.

Always monitor glucose in patients with insulin-dependent diabetes mellitus (IDDM) and non–insulin-dependent diabetes mellitus (NIDDM) because encainide may exacerbate hyperglycemia by unknown mechanism.

Flecainide - Class IC

After ABCs are stabilized, early (within 1 h) gastric emptying is recommended. Secure airway before this step because seizures can occur within 2 hours of ingestion or overdose.

Hemodialysis and hemoperfusion have not been effective in overdose therapy. Intravenous sodium bicarb, 100 mEq over 5 minutes, followed by continuous infusion to maintain a serum pH of 7.5-7.55 reversed hypotension and resulted in narrowing of the QRS complex in isolated case reports.

Propafenone - Class IC

Once the airway is secured via an endotracheal tube (ETT), gastric emptying may be done to reduce amount absorbed. Activated charcoal may be used, although no evidence suggests that this actually helps to decrease toxicity.

Supportive measures are the only therapy because hemodialysis and hemoperfusion are not useful and no antidote is available.

Sodium lactate has been used to theoretically load sodium channels, thus improving the widening of the QRS interval. Diazepam is the drug of choice for seizures. Pressors and pacers are indicated for cardiac support.

Ajmaline, cibenzoline, detajmium - Class IC

Establishment of ABCs is priority, including installation of a temporary transvenous pacemaker before gastric decontamination because vagal stimulation can worsen existing bradyarrhythmias.

Supportive measures are the only therapy because hemodialysis and hemoperfusion are not useful and no antidote is available.

Amiodarone - Class III

GI decontamination is useful because of slow oral absorption; activated charcoal decreases amiodarone absorption. Patients should be responsive to supportive measures as described with other drugs. If bradycardia occurs, use a pacemaker or beta-adrenergic agonist.

Consider cholestyramine to decrease the enterohepatic recirculation of amiodarone. Corticosteroids have been used to increase recovery after pulmonary toxicity.

Bretylium - Class III

Treatment is supportive and symptomatic. Bretylium is dialyzable, but limited experience with this method of treatment exists in literature.

N-acetyl procainamide - Class III

Airway, circulatory support, IV access, and ECG monitoring are of paramount importance. Implement supportive measures.

GI decontamination and activated charcoal within 3-4 hours are indicated following an oral overdose.

Intoxication may be responsive to hemodialysis, or inline hemodialysis/hemoperfusion may decrease levels more rapidly.

Sotalol - Class III

Treatment is supportive and symptomatic. See Torsade de pointes treatment below for therapy. Bradycardia of hypotension not responding to atropine or pacing may respond to glucagon.

Ibutilide and dofetilide - Class III

Treatment still is under investigation; however, suggestions for management include correction of hypokalemia and hypomagnesemia. Cardioversion or pacing may be helpful for arrhythmias.

Adenosine

Treatment is supportive and symptomatic. Have external pacing available while using adenosine. Be prepared for transient AVB.

One report states that theophylline may alleviate chest pain induced by adenosine in patients with ischemic heart disease.

Torsade de pointes treatment

Torsade de pointes is a common proarrhythmia, aggravation, or provocation of arrhythmias provoked by antidysrhythmic agents. Risk factors for this include toxic blood levels (due to advanced age or renal, hepatic, or heart disease), severe ventricular dysfunction (ejection fraction [EF] < 35%), serious presenting arrhythmia, concomitant digoxin therapy, hypokalemia or hypomagnesemia, and certain drug combinations (eg, class IA + class IA, class IA + class III, or class IA + TCAs).

Torsade de pointes generally occurs immediately after precipitating drug therapy has begun; therefore, discontinuing drug therapy is very important. Intravenous magnesium and temporary atrial or ventricular overdrive pacing suppresses the ventricular tachycardia; ventricular tachycardia usually does not recur after terminating the pacer. Isoproterenol can be used to increase heart rate cautiously until pacer is placed. Magnesium is an effective and safe for treatment of torsade de pointes. A study by Tzivoni et al (1984-1988) demonstrated the termination of torsade de pointes within 5 minutes after administering magnesium using the following dosages:^[2]

• Step 1: Administer 2 g bolus of magnesium sulfate over 3-5 minutes.
• Step 2: Repeat 2 g bolus of magnesium if partial response is observed within 10-15 minutes.
• Step 3: Infuse 2-10 mg/min if no torsade de pointes is present but premature ventricular contractions (PVCs) continue.
• Step 4: Treat with overdrive pacing or isoproterenol if torsade de pointes continues.

• Consult with a medical toxicologist and/or a regional poison control center for acute toxicity.
• Consult with a cardiologist for long-term plans to continue intensive monitoring in cardiac unit.