Antidysrhythmic Toxicity Treatment & Management
- Author: Nidhish Sasi, MD; Chief Editor: Asim Tarabar, MD more...
Airway, breathing, and circulatory support (ABCs); intravenous (IV) access; and electrocardiographic (ECG) monitoring are of paramount importance. Emergency medicine physicians should arrange with cardiology or toxicology service for admission of the patient to a monitored bed in cardiac unit.
Consult with a medical toxicologist and/or a regional poison control center for acute toxicity. Consult with a cardiologist for long-term plans or to continue intensive monitoring in a cardiac unit.
Treatment measures and the drugs for which they are appropriate are as follows (for more details on each agent, refer to each individual section).
Sodium bicarbonate is indicated for patients with a widened QRS complex. Closely monitor for resultant alkalemia, hypokalemia, and hypomagnesemia. Because disopyramide blocks calcium channels, administration of calcium may help treat hypotension. Patient with disopyramide-induced symptoms of overt heart failure may benefit from diuretics, inotropic agents, or afterload-reducing drugs. IV magnesium sulfate may be used to treat QT prolongation and torsades de pointes. 
GI decontamination is sometimes warranted to decrease GI disopyramide absorption, because of its anticholinergic effects. Hemodialysis is effective in decreasing the serum half-life and may be useful as second-line therapy when supportive care is not effective.[39, 40]
Implement supportive care. Orogastric lavage and activated charcoal should be considered for oral overdoses. If renal failure is present, consider hemodialysis, although its value in this setting has not yet been confirmed. Avoid other QT interval–prolonging agents. Avoid the class IA antidysrhythmics quinidine and disopyramide, due to prodysrhythmic and QT interval–prolonging effects. Consider early pacemaker placement in patients with increasing atrioventricular block. Ventricular tachycardia or fibrillation in the setting of Brugada syndrome is best managed with isoproterenol rather than amiodarone. Mechanical ventilation may be required for acute but rare respiratory compromise due to myasthenia gravis–like syndrome or myositis.
In the setting of acute cardiotoxicity with QRS interval widening, hypertonic sodium bicarbonate is indicated. Symptomatic bradycardia may require placement of a temporary pacemaker. In patients with hypotension, blood pressure should be supported with normal saline and vasopressors. Dysrhythmias may be treated with a class IB agent.
After intravenous access, oxygen, and cardiac monitoring are initiated, seizures should be treated with benzodiazepines. Check serum glucose and electrolyte levels such as calcium if seizures are not responsive.
Orogastric lavage and activated charcoal shoudl be considered for gastrointestinal decontamination.
Correct imbalances of electrolytes (eg, potassium, calcium) and glucose. Due to its very large volume of distribution, quinidine is not amenable to dialysis. Experience with charcoal hemoperfusion is limited. Glucagon has been proven useful in animal models but such data are lacking in humans.
Benzodiazepines are the first-line treatment for seizures due to lidocaine overdose. Providers should avoid phenytoin, which is another 1B sodium-channel blocker and could worsen toxicity.
Phenobarbital, propofol, and thiopental have also been reported to succesfully treat local anesthetic lidocaine–induced CNS toxicity, including seizures and muscle twitching.
In benzodiazepine-refractory seizures, providers should escalate care with propofol or a barbiturate, a neuromuscular antagonist, and endotracheal intubation, because acidosis will potentiate lidocaine toxicity. For severe acidosis, treat with sodium bicarbonate.
Intravenous infusion of lipid emulsions should be considered for severe toxicity.
Cardiopulmonary bypass has been used to treat cardiac arrest secondary to lidocaine toxicity. Amiodarone is the recommended agent to treat defibrillation. Avoid other class IB antiarrhythmics, as well as class II and class IV agents, during lidocaine-induced cardiac arrest.[41, 42]
No specific antidotes are available for mexiletine. Active charcoal after recent ingestion may be appropriate. A portion of ingested mexiletine is bound to low molecular weight plasma proteins, and hemodialysis has been shown to be associated with improvement in vital signs when supportive care with intravenous fluids and vasopressors has failed.
Intravenous sodium bicarbonate, 100 mEq over 5 minutes, followed by continuous infusion to maintain a serum pH of 7.5-7.55, has reversed hypotension and resulted in significant narrowing of the QRS complex. Urine alkalinization may reduce renal clearance; hypertonic sodium chloride might theoretically provide a better therapeutic effect. Hyponatremia should be corrected.
Intravenous fat emulsion has been shown to treat life-threatening flecainide overdose in case reports.
Cardiopulmonary bypass and extracorporeal membrane oxygenation have been reported and may be reasonable if available in cases of severe toxicity refractory to supportive measures.
Electrolyte management is crucial in flecainade toxicity because hyponatremia can increase toxicity. [46, 47]
Sodium bicarbonate is recommended for cardiotoxicity with a widened QRS complex, as it has been shown to narrow QRS complexes. Glucagon may be indicated for excessive beta blockade effect such as bradycardia.
Supportive treatment with intravenous fluids and inotropic and vasopressor support is indicated for hypotensive patients. Temporary pacing for bradycardia was effective for improving hemodynamics in a case report.
Gastric lavage is useful in patients with severe recent toxic ingestions.
Multiple-dose activated charcoal may be helpful following overdose. If bradycardia occurs, use a pacemaker or beta-adrenergic agonist. In cases of acute pulmonary toxicity, oral steroids may help. Intubation and supportive care are necessary if severe pulmonary toxicty or an acute respiratory distress (ARDS) presentation occurs.
Amiodarone and its metabolite are not dialyzable. Given its long half-life (25-100 days), toxicity may continue despite cessation of treatment.
Treatment is supportive. Heart failure may be treated with inotropes and diuretics. Pulmonary toxicity such as pneumonitis or organizing pneumonia may respond to steroids and not antibiotics. Rare fulminant hepatic failure may necessitate liver transplantation. Whether dronedarone and its metabolites can be removed by dialysis remains unknown.
Treatment is supportive and symptomatic. Hemodialysis is helpful in reducing plasma concentrations. See Torsade de Pointes Treatment, below.
Prophylactic administration of magnesium in high doses may increase the safety and efficacy of ibutilide in converting atrial fibrillation. Supportive and resuscitative measures should be available for cardiac arrest from ventricular dysrhythymia due to ibutilide.
Activated charcoal should be considered after a recent ingestion. Consider repletion of potassium and magnesium and supplementation of magnesium. See Torsades de Pointes Treatment, below.
External pacing pads should be available during adenosine administration. The short half-life of adenosine limits the duration of adverse effects in most cases.
Torsade de Pointes Treatment
Torsades de pointes generally occurs immediately after drug therapy has begun; drug infusion should immediately be stopped. Magnesium in a 2-g bolus should be administered. Overdrive pacing and isoproterenol should also be considered as therapeutic actions if torsade de pointes persists.
Lipid Emulsion Therapy
Intravenous lipid emulsion (ILE) therapy has demonstrated efficacy as a life-saving antidote for cardiotoxicity from local anesthetics, with the best evidence for bupivicaine toxicity. Postulated mechanisms of action include the creation of a lipid compartment that takes unbound, lipophilic drugs out of the plasma, improving the delivery of energy substrates to myocardial mitochondria, and increasing the intracellular myocyte calcium concentration (thereby augmenting inotropy).
There is some evidence of ILE efficacy for beta-blocker and calcium channel blocker overdose.[52, 53] Flecainide overdose has also been treated successfully with ILE. This approach may be considered for amiodarone overdose, given that drug's high degree of lipophilicity and partitioning into the lipid emulsion compartment.
The recommended dose for local anesthetic toxicity (unlabeled use) is a bolus of 20% intralipid/fat emulsion at 1.5 mg/kg administered over 1 minute, followed by an infusion of 0.25 mL/kg/minute. The bolus dose can repeated 1-2 times, and the infusion rate can be increased to 0.5 mL/kg/minute. Infusion should be continued for 10 minutes after hemodynamic stability is restored.
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