Antidysrhythmic Toxicity

Updated: May 17, 2022
Author: Nidhish Sasi, MD; Chief Editor: Michael A Miller, MD 


Practice Essentials

Antidysrhythmic medications are widely used to treat or prevent abnormalities in cardiac rhythms. They accomplish this through a number of mechanisms involving automaticity or ion channel dynamics, which in turn affect the propagation of the myocardial electrical impulse via change in conduction velocity or refractory period.

Antidysrhythmics alter the propagation and mechanisms of cardiac rhythms, making toxicity from these agents highly lethal. In fact, antidysrythmics can be prodysrhythmic at both therapeutic and toxic serum concentrations. Additionally, the patients receiving these drugs may have a lower dysrhythmic threshold resulting from underlying cardiac conditions as well as other comorbidities, making them more suscpetible to toxicity. A thorough knowledge of this class of drugs is necessary for differentiating drug toxicity from primary disease.

See also Beta-Blocker Toxicity and Calcium Channel Blocker Toxicity, as those topics are not covered in this article. 

Signs and symptoms

Toxicity from antidysrhythmic agents can be grouped in terms of clinical presentation and electrocardiographic (ECG) abnormalities, as follows:

  • Anticholinergic syndromes: Procainamide, disopyramide, quinidine
  • Heart failure: Disopyramide, flecainide, propafenone, sotalol, procainamide
  • Hypotension: Quinidine, procainamide, amiodarone, dronedarone, lidocaine, mexiletine, flecainide, propafenone, ibutilide
  • CNS symptoms: Quinidine, procainamide, disopyramide, lidocaine, mexiletine, flecainide, propafenone
  • Seizures (acute toxicity): Quinidine, procainamide, lidocaine, mexiletine, flecainide, propafenone
  • Endocrine dysfunction: Amiodarone (hypothyroidism or hyperthyroidism), quinidine and disopyramide (hypoglycemia)
  • Hematology/Oncology: Amiodarone (hepatic/biliary malignancy), procainamide (blood dyscrasia)
  • Pulmonary/autoimmune: Procainamide (lupuslike syndrome, vasculitis), amiodorone (fibrosis, pneumonitis)
  • CNS: procainamide, lidocaine, mexilitine
  • Dermatologic: procainamide, propafenone

ECG changes are as follows:

  • QRS widening: Quinidine, procainamide, disopyramide, flecainide, propafenone, amiodarone, dronedarone
  • PR prolongation: procainamide
  • QTc prolongation: Quinidine, procainamide, disopyramide, amiodarone, dronedarone, sotalol, ibutilide, dofetilide; slight prolongation with flecainide, propafenone
  • Ventricular arrythmia (ventricular premature contractions or ventricular tachycardia): Procainamide
  • Torsade de pointes: Ibutilide, dofetilide, sotalol, quinidine, procainamide, disopyramide

See Clinical Presentation for more detail.


The first and most important diagnostic tool in acute antidysrhythmic toxicity is electrocardiography. ECG changes such as QRS widening, QTc prolongation, and atrioventricular block should be ruled out.

Serum electrolytes concentrations should be obtained, especially in patients taking antidysrhythmics that prolong the correct QT (QTc) interval.

Serum drug concentrations are not likely to be helpful to the emergency physician treating a patient with acute antidysrhythmic drug toxicity, but concentrations of quinidine, lidocaine, and propafenone can be measured in the acute care setting.

Chest radiographs and brain natriuretic peptide levels should be obtained in patients presenting with heart failure symptoms; Chest radiographs should also be obtained in patients taking amiodarone or dronedarone and presenting with pulmonary symptoms.

Thyroid function tests should be obtained in patients taking amiodarone or dronedarone who present with signs and symptoms of hypothyroidism or hyperthyroidism.

See Workup for more detail.


Airway, breathing, and circulatory support; intravenous access; and ECG monitoring are of paramount importance. Treatment measures and the drugs for which they are appropriate are as follows:

  • GI decontamination: Should be considered in most antidyrthymmic overdose, and specifically with disopyramide, quinidine, flecainide, propafenone, amiodarone
  • Hemodialysis: Procainamide, mexiletine, sotalol
  • Sodium bicarbonate: Class Ia and Ic antidysrhythmics (quinidine, procainamide, disopyramide, lidocaine, mexiletine, flecainide, propafenone)
  • Magnesium: Class III agents, Ibutilide, dofetilide, sotalol, quinidine, procainamide, disopyramide
  • Intravenous lipid emulsion: Verapamil; less evidence for lidocaine, flecainide, amiodarone
  • Seizure control (benzodiazepines): Quinidine, procainamide, lidocaine, mexiletine, flecainide, propafenone

See Treatment and Medication for more detail.


Despite the advent of interventional techniques such as catheter ablation and the implantable cardioverter-defibrillator in the treatment of supraventricular and ventricular tachycardia, antidysrhythmic drugs continue to play a significant role in treating and suppressing life-threatening dysrhythmias. The prodysrhythmic effects of many of these drugs also continue to present a major clinical problem, especially in the growing population of patients with underlying heart failure.

When encountering a patient with dysrhythmias on antidysythmic drugs, the physician must maintain a broad differential diagnosis that includes not only drug toxicity but underlying ischemia, structural cardiac abnormalities, and conduction disturbances. Thus, understanding the adverse effects and electrocardiographic profiles of antidysrhythmic agents is critical for diagnosis and treatment of possibly life-threatening drug toxicity.

This article discusses the major antidysrhythmic drugs within classes I, III and V, with specific attention to their adverse effects and clinical presentations in the setting of acute toxicity. Toxicity from class II and IV dysrhythmics is discussed elsewhere (see Beta-Blocker Toxicity and Calcium Channel Blocker Toxicity)

For additional information, see Medscape's Cardiology Resource Center. For patient education resources, see the First Aid and Injuries Center, as well as Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.


Most antidysrythmics may be categorized via the Vaughan-Williams classification system, based on their mechanism of activity (see the image below). Medications used to treat arrhythmias that have variable mechanisms have been included in class V; these include magnesium, digoxin, and adenosine. The Vaughn-Williams classes are as follows:

  • Class I: Sodium channel blockers
  • Class II: Beta-adrenergic blockers
  • Class III: Potassium channel blockers
  • Class IV: Calcium channel blockers
  • Class V: Other or unknown mechanism of action
Schematic of the cardiac action potential. Phase 0 Schematic of the cardiac action potential. Phase 0 depicts the the influx of sodium ions. Phases 1 and 3 correspond to the sodium-channel inactivation and the repolarizing eflux of potassium ions, respectively. Phase 2 depicts the opening of voltage-sensitive calcium channels causing a plateau in voltage.

Class I agents bind sodium channels reducing depolarization rate, which serves to slow and reduce the rate of rise of the action potential (phase 0). They also help to inhibit depolarization of neuronal cells, which provides local anesthesia. Class I agents also inhibit depolarization in atrial, ventricular, and Purkinje myocytes, thereby decreasing conduction velocity and automaticity.

Class I agents are further categorized into A, B, or C subclasses, based on the degree of sodium channel blockade and effects on repolarization, as follows:

  • Class IA agents: Prolong repolarization and action potential through blockade of outward rectifying potassium channels; moderate slowing of cardiac conduction, prolong both the QRS and QTc intervals

  • Class IB agents: Bind to the sodium channel in its inactivated state; shorten action potential duration and selectively depress cardiac conduction in ischemic cells; generally do not prolong the QRS interval

  • Class IC agents: Bind to sodium channels in the active state and are slow to release from sodium channels; decrease rate of rise of phase 0 of the action potential leading to prolonged QRS interval; have little effect on action potential duration but markedly depress cardiac conduction

Class II agents indirectly blockade calcium channel opening by attenuating adrenergic activation. These agents block the proarrhythmic effects of catecholamines.

Class III agents prolong refractoriness and delay repolarization by blocking potassium channels (phase 2, phase 3) leading to prolonged QTc intervals on the ECG. They have little direct effect on sodium channels.

Class IV agents slow sinoatrial node pacemaker cell and atrioventricular conduction by direct blockade of L-type voltage-gated calcium channels.



Class IA antidysrhythmics


In addition to sodium and potassium channel blockade, disopyramide is a muscarinic antagonist. See the following:

  • Indications: Documented ventricular dyshythmias, atrial dysrhythmias in patients with hypertrophic cardiomyopathy (unlabeled use)

  • Dosages: Dose adjustment is gradual; 100-200 mg orally every 6 hours; reduced dosage frequency recommended in renally impaired patients

  • Metabolism: Metabolized by the liver (CYP3A4), 40-60% excreted by the kidneys

  • Therapeutic concentrations: Atrial dysrhythmias at 2.8-3.2 mcg/mL, ventricular dysrhythmias at 3.3-7.5 mcg/mL, toxic level at >7 mcg/mL

  • Drug interactions: Drugs that also prolong the QTc interval should be avoided, as torsade de pointes can occur with coadministration; drugs that interfere with CYP3A4 hepatic metabolism of disopyramide include ketoconazole, isoniazid, erythromycin, phenytoin, rifampin, verapamil and protease inhibitors used for HIV infection; disopyramide may enhance anticholinergic effects of anticholinergic agents, such as dry mouth, urinary retention, and constipation. Disopyramide also possesses strong negative inotropic activity and should be avoided in those with left ventricular dysfunction. as well as those taking β-blockers.[1]


Procainamide blocks sodium and potassium channels, and its active metabolite prolongs the action potential duration of ventricular myocytes and Purkinje fibers. It is available in oral, intramuscular (IM), and intravenous (IV) forms. See the following:

  • Indications: Supraventricular or ventricular dysrhythmias

  • Dosages - Loading dose IV: 15-18 mg/kg over 30 minutes IV or 20-50 mg/minute or 100 mg every 5 minutes until dysrhythmia controlled, QRS widens to 50% its original width, hypotension occurs, or maximum of 17 mg/kg has been given; IV maintenance dose is 1-4 mg/min; IM: 0.5-1 g every 4-8 hours; toxicity may occur if dose is not reduced in patients with renal or hepatic impairment; oral form is not available in the United States

  • Metabolism: Metabolized in the liver by acetylation into a metabolite that prolongs the action potential; both procainamide and its metabolite are excreted by the kidneys

  • Therapeutic concentrations: 4-10 µg/mL; toxic concentration at >10-12 µg/mL; severe toxicity when serum concentrations >60 µg/mL[2]

  • Drug interactions: Anticholinergic drugs produce additive vagolytic effects; QTc prolongation can become more severe when patients are taking other QTc-prolonging drugs; cimetidine increases drug levels of procainamide by interfering with its hepatic metabolism

Procainamide should be avoided in patients with myasthenia gravis.


In addition to blocking sodium and potassium channels, quinidine blocks alpha-adrenergic receptors and muscarinic receptors. Quinidine has the same antimalarial and antipyretic properties as quinine; in addition to its cardiologic indications, it is used for treatment of malaria, and as an illicit abortifacient. See the following:

  • Indications: Suppression of atrial and ventricular dysrhythmias; quinidine has shown effective antiarrhythmic activity in patients with Brugada syndrome[3]

  • Test dose: Test dose of 200mg quinidine sulfate several hours before full dosage

  • Maintenance dose: quinidine sulfate 200-400mg PO q6-8hr or 600mg of SR PO q8-12hr

  • Maintenance dose: quinidine gluconate 648mg PO q12hr OR 324-660mg PO q8hr

  • Metabolism: Hepatic elimination is responsible for 60-80%, whereas renal elimination is responsible for 20-40%

  • Therapeutic concentrations: 2-6 mg/L or 6.2-18.5 µmol/L by assay; concentrations >14 µg/mL are associated with toxicity

  • Drug interactions: Cimetidine and ketoconazole elevate the quinidine serum concentration; verapamil impairs hepatic metabolism, quinidine increases digoxin concentration

Risk factors for quinidine toxicity are hepatic disease, renal insufficiency, and heart failure. Quinidine can cause sinus node depression in patients with sick sinus syndrome.

Class IB antidysrhythmics


Lidocaine is a derivative of cocaine that blocks fast sodium channels, leading to a modest reduction in the rate of phase 0 depolarization. See the following:

  • Indications: Ventricular dysrhythmias; local anesthetic; no longer used to prevent dysrhythmias immediately following myocardial infarction, with amiodarone being the preferred agent[4]

  • Dosages: Initial bolus of 1 mg/kg at a rate of 20-50 mg/min, then 0.5 mg/kg, 20-40 minutes later; maintenance infusion rate of 1-4 mg/min

  • Metabolism: Hepatic metabolism by CYP3A4 to an active metabolite; toxicity more likely to occur in patients with reduced hepatic blood flow (eg, from shock, low cardiac output) or hepatic dysfunction (eg, cirrhosis)

  • Therapeutic concentrations: Toxic concentrations at >5 µg/mL; severe toxicity when concentrations >10 µg/mL

  • Drug interactions: CYP3A4 inhibitors such as cimetidine and amiodarone increase risk of lidocaine toxicity; beta-blockers, especially nonselective ones such as propranolol, may reduce hepatic blood flow, leading to decreased clearance of lidocaine and increased drug effect

The therapeutic index of lidocaine is narrow. Toxicity may occur while a clinician is trying to achieve adequate local or regional anesthesia for repairing large lacerations or from pediatric ingestion of viscous lidocaine. Patients at greatest risk for iatrogenic toxicity are those with poor cardiac output or hepatic disease. Toxicity is potentiated in acidemic states (eg, hypercapnia during rapid sequence intubation, lactic acidosis following seizure).[5]


Mexiletine is clinically equivalent to lidocaine in its mechanism of slowing the rate of phase 0 depolarization by blocking fast sodium channels, and it shortens the action potential duration of Purkinje fibers.  It blocks the late sodium current, which may be useful for preventing delayed ventricular repolarization and torsade de pointes in long QT syndrome.[6]

  • Indications: Ventricular dyshythmias, neuropathic pain, myotonia

  • Dosages: 200-300 mg every 6-8 hours; dosage should be reduced in patients with hepatic dysfunction or heart failure due to decreased clearance

  • Metabolism: Rapidly absorbed by the small intestine and undergoes hepatic, primarily CYP2D6, metabolism; patients with decreased hepatic blood flow are at increased risk for toxicity; 10% of mexiletine is eliminated unchanged by the kidneys; urine alkalization slows renal elimination

  • Therapeutic concentrations: 0.5-2 µg/mL; toxic concentration at >2 µg/mL

  • Drug interactions: Cimetidine increases risk of toxicity. Selective serotonin reuptake inhibitors may decrease mexiletine clearance and promote toxicity. [7]

Class IC antidysrhythmics


Flecainide has a strong blocking effect on the rapid sodium channel, decreasing the rate of depolarization. Flecainide also slows conduction in all cardiac fibers, making it contraindicated in patients with second degree atrioventricular block and intraventricular conduction delay. In high concentrations, flecainide may block slow calcium channels and have negative inotropic effects. See the following:

  • Indications: Supraventricular dysrhythmias (primarily paroxysmal atrial fibrillation) and ventricular dysrhythmias; however, was shown to increase dysythymias and mortality in the post-MI period and those with depressed LV function and history of ventriclar dysrythmias; also used to help diagnose or possibly treat certain congential dysryhtmia disorders such as Brugada and LQT3 syndrome.[8, 9]

  • Dosages: Starting dose 100 mg every 12 hours, not to exceed 400 mg/day; some recommend initiating therapy as an inpatient to monitor for dysrhythmias

  • Metabolism: 75% undergoes hepatic CYP2D6 metabolism; 25% is renally eliminated

  • Therapeutic concentrations: 0.2-1 mg/mL

  • Drug interactions: May increase serum concentrations of digoxin and propranolol; drugs such as paroxetine, fluoxetine, quinidine, amiodarone, propranolol, and ritonavir can increase flecainide concentrations by affecting CYP2D6 metabolism. Should be avoided with beta blockers due to concomitant AV nodal suppression and negative inotropy. Concomitant thiazide and flecainaide use predisposes patients to hyponatremia which can inturn precipitate flecainaide toxicity. 

Patients at risk for flecainide toxicity include those with renal insufficiency, decreased hepatic flow from compromised cardiac output, hyponatremia, and those taking medications that undergo CYP2D6 metabolism. 


In addition to blocking fast sodium channels, propafenone is a weak beta-adrenergic antagonist and calcium channel blocker. See the following:

  • Indications: Atrial fibrillation and life-threatening ventricular dysrhythmias

  • Dosages: 150-300 mg every 8 hours, not to exceed 1200 mg/day; dose increases should be made at intervals of 3-4 days; sustained-release dosing is 225-425 twice daily; single dose of 600 mg may be used for the acute pharmacologic cardioversion of paroxysmal atrial fibrillation (unlabeled use)

  • Metabolism: Hepatic metabolism by CYP2D6 (predominantly), CYP3A4, and CYP1A2; genetic polymorphisms in CYP2D6 result in variable metabolism rates

  • Therapeutic concentrations: 200-500 ng/mL

  • Drug interactions: Increases serum concentrations of warfarin, digoxin, propranolol, and metoprolol; drugs that inhibit CYP2D6 or CYP3A4 can increase serum levels of propafenone

Patients at risk for propafenone toxicity include those with a polymorphism of CYP2D6 that slows metabolism, patients with hepatic dysfunction, and those taking drugs that interfere with CYP2D6 metabolism. Similarly to flecanaide, patients with structural heart disease and/or those being treated for ventricular rather than supraventricular arrhythmias are at higher risk for concerning severe cardiovascular complications such as arrtyhmia and cardiac arrest. 

Class III antidysrhythmics


Amiodarone blocks fast sodium channels, beta-receptors, L-type calcium channels, and delayed rectifier potassium channels. It prolongs the effective refractory periods of all cardiac tissue. Additionally, amiodarone inhibits the conversion of thyroxine to triiodothyronine. See the following:

  • Indications: Supraventricular and life-threatening ventricular dysrhythmias; atrial fibrillation prophylaxis following open heart surgery (unlabeled use)

  • Dosages: Intravenous, 150 mg over 10 minutes followed by 1 mg/min for 6 hours and 0.5 mg/min for the remaining time; oral, start with 800-1200 mg/day for the first 3 weeks (given once or twice daily) and reduce to 400 mg/day for several weeks to a maintenance dose of 300 mg or less per day

  • Metabolism: Minimal first-pass effect, excreted largely in bile; metabolized by CYP3A4 to desethylamiodarone, an active metabolite with an antidysrhythmic effect; this metabolite undergoes hepatic metabolism; onset of action after oral administration is delayed by several days

  • Therapeutic concentrations: 1-2.5 mg/mL

  • Drug interactions: concentrations are increased by digoxin, diltiazem, quinidine, procainamide, oral anticoagulants, and phenytoin; international normalized ration should be closely monitored in patients taking amiodarone and warfarin; amiodarone inhibits cytochrome enzymes and transport proteins (p-glycoprotein); QTc-prolonging drugs that undergo metabolism to these proteins can add to prolongation of the QTc interval; may enhance bradycardia in patients on beta-blockers; may also increase serum concentration of dabigatran etexilate

Amiodarone is well known to cause thyroid, liver, and pulmonary toxicity. It also has adverse CNS and skin side effects. 


Dronedarone is a noniodinated derivative of amiodarone, and like amiodarone it inhibits sodium channels, potassium channels, L-type calcium channels, and beta-receptors. Dronedarone also inhibits alpha1 receptors. Dronedarone is thought to cause less lung, liver, and thyroid toxicity than amiodarone. Use of this drug is contraindicated in any patient with an ejection fraction of less than 35% or class IV heart failure. See the following:

  • Indications: Atrial and ventricular dysrhythmias; maintenance of sinus rhythm in patients with atrial flutter or fibrillation and no significant cardiovascular disease; atrial fibrillation in patients with hypertrophic cardiomyopathy (unlabeled use)

  • Dosages: 400 mg twice daily

  • Metabolism: Hepatic metabolism by CYP3A4 to active and inactive metabolites

  • Therapeutic concentrations: 84-167 ng/mL

  • Drug interactions: Digoxin, beta-blockers, calcium channel blockers, any agent that prolongs QT; CYP3A4 inhibitors (azoles, cyclosporine, clarithromycin, ritonavir) may increase dronedarone toxicity; may increase international normalized ratio in patients taking warfarin; can significantly increase statin concentrations

Hepatic dysfunction increases the risk of dronedarone toxicity. Higher mortality has been shown when dronedarone is given to patients with New York Heart Association class III or IV heart failure. Cases of interstial pneumonitis or bronchiolitis obliterans with organizing pneumonia (BOOP) have been reported in dronedarone users.[10]

Despite a small increase in serum creatinine levels due to inhibition of tubular secretion, dronedarone does not impact the glomerular filtration rate and overall renal function, although it may affect the renal clearance of other medications and should be monitored in patients with preexisting renal dysfunction or on nephrotoxic medications. Furthermore renal failure may occur in setting of worsening heart failure due to dronedarone.[11]


Sotalol is a nonselective beta-adrenergic antagonist that prolongs the action potential and effective refractory period by blocking potassium channels. See the following:

  • Indications: Ventricular dysrhythmias, atrial fibrillation, atrioventricular (AV) nodal reentrant tachycardia, AV tachycardia

  • Dosages: IV, 75-150 mg infused over 5 hours, twice daily (not to exceed 300 mg twice daily); oral, 80-160 mg twice daily, dose may be increased gradually to 240-320 mg/day; dose adjustment should be made based on degree of renal impairment

  • Metabolism: 90-100% absorption with 100% bioavailability and no metabolism; renally excreted as an unchanged drug; baseline creatinine clearance should be measured before initiating therapy and dosage should be adjusted based on degree of renal insufficiency

  • Therapeutic concentrations: 1-4 mg/mL

  • Drug interactions: Avoid use with other QTc-prolonging drugs; bradycardia or AV block may occur if patients are concurrently taking calcium channel blockers. Hypotension may occur with concomitant use with  adrenergic antagonists. On the other hand, significant hypertension has been reported with concomitant clonidine usage. Antacids containing magnesium or aluminum salts may reduce sotalol bioavailability.[12, 13]

Patients at risk for toxicity are those with renal dysfunction, with concomitant use of QTc-prolonging drugs, and women.[14]  


Ibutilide blocks the delayed rectifier potassium channel, prolonging repolarization. It also activates the slow inward sodium current. Ibutilide increases the refractory period of the accessory pathway, the His-Purkinje system, and the AV node.  See the following:

  • Indications: Acute termination of atrial fibrillation or flutter in patients with normal heart function/structure, as well as posteroperative cardioversion; used as pretreatment in electrical cardioversion as well as in atrial fibrillation in Wolff-Parkinson-White syndrome

  • Dosages: 1 mg IV over 10 minutes; a second 1-mg dose may be given after the first dose is finished if dysrhythmia persists

  • Metabolism: Hepatic

  • Drug interactions: Avoid other QTc-prolonging drugs

The primary concern of ibutilide toxicity is its QT prolongation and increased risk for torsade de pointes.[15]


Dofetilide prolongs the refractory period by blocking the delayed rectifier current. This drug effect is stronger in atrial than in ventricular tissue. See the following:

  • Indications: Conversion of atrial fibrillation or flutter to sinus rhythm; suppression of recurrent atrial fibrillation

  • Dosages: Oral doses of 0.125-0.5 mg twice daily; reduce dose in patients with reduced renal function

  • Metabolism: 50% excreted unchanged in urine; remainder undergoes hepatic metabolism (CYP3A4)

  • Drug interactions: Interactions with cimetidine, verapamil, ketoconazole, hydrochlorothiazide, prochlorperazine, megestrel, and trimethoprim have been documented

Patients at risk for toxicity are those with renal impairment, congenital long QT syndrome, electrolyte derangements (ie, hypocalcemia, hypomagnesemia, hypokalemia), and concurrent therapy with other QTc-prolonging drugs and drugs that inhibit the renal cation transport system.[16]

Class V antidysrhythmics


Adenosine is an extracellular signaling molecule that induces a short-duration heart block when used intravenously. Adenosine increases potassium conductance and shortens the atrial action potential duration and hyperpolarizes the myocyte membrane potential. Adenosine slows conduction in the AV node. See the following:

  • Indications: Supraventricular tachycardias (SVTs), after failure of vagal maneuvers

  • Dosages: 3 mg initial dose recommended when administered through a central venous line, to a heart transplant patient, or in patients on comcomitant dipyridamole or carbamazepine; otherwise 6-mg initial dose by rapid peripheral IV push is recommended, followed by 12 mg and another 12 mg if SVT is not broken; higher doses may be needed for patients taking methylxanthines (eg, theophylline, caffeine)

  • Metabolism: Intracellularly metabolized or phosphorylated

  • Drug interactions: Effects are antagonized by methylxanthines and potentiated by dipyridamole and carbamazepine

Adenosine is contraindicated in patients with sick sinus syndrome, second- and third-degree AV block, and atrial fibrillation down an accessory pathway (Wolff-Parkinson-White syndrome).


In 2020, 1185 single exposures to antiarrhythmic drugs were reported to US poison control centers. Most exposures involved adults. There were 31 exposures resulting in major toxicity and 5 deaths.[17]

Antidysrhythmic toxicity generally affects both sexes equally. However, with sotalol some studies have found that females are at higher risk for dysrhythmia (especially for torsade de pointes).[14]

Prodysrhythmic effects occur more frequently in patients with underlying heart failure.

Older patients, in general, have a higher risk for the development of dysrhythmias than younger patients. Drug-to-drug interactions are increasing, especially in elderly patients taking multiple antiarrhythmic drugs simultaneously.




As in the case of any patient with suspected or known acute poisoning, attempt to obtain the following:

  • Original medication containers
  • Pill counts
  • The number of pills that may have been ingested
  • Approximate time of ingestion
  • A report of any potential co-ingestants

Family members or emergency medical services personnel should bring all the patient’s medications to the emergency department to help the clinician determine the source of toxic manifestations. Eliciting a history of co-ingestants is important because these can obscure the clinical picture.

In patients with prescribed antidysrhythmic agents, attempt to differentiate manifestations of primary disease from possible toxic effects of the drug by asking the following questions:

  • What were the indications for starting the drug?
  • If the patient does not know, will a call to the prescribing physician or a review of the medical record help?
  • How long has the patient been taking this drug?
  • How do the patient's symptoms correlate with the initiation of drug therapy?
  • Is the patient compliant with the drug therapy?
  • Has the patient taken any extra doses?
  • Has the patient added any new drugs recently?
  • Is the patient taking any nonprescription drugs?

Adverse Effects of Individual Agents Unrelated to Cardiac Conduction


The anticholinergic property of disopyramide leads to the following adverse effects:

  • Urinary hesitancy or retention
  • Constipation
  • Dry mouth
  • Blurred vision
  • Bloating

Disopyramide may also cause headache, muscle weakness, nausea, and fatigue. Patients with preexisting ventricular dysfunction or on beta blockade may report symptoms of heart failure, including dyspnea, edema, and decreased exercise tolerance. Disopyramide is also known to cause hypoglycemia, through unclear mechanisms.[1]


Adverse effects that patients may report include gastrointestinal (GI) symptoms such as nausea, vomiting, and diarrhea; bitter taste; and neuropsyciatric symptoms such as headache, insomnia, dizziness, psychosis, hallucinations, and depression.

Long-term use of procainamide is associated with the development of antinuclear antibodies and drug-induced systemic lupus erythematosus (SLE) syndrome characterized by arthralgias, myalgias, rash, fever, vasculitis and Raynaud phenomenon. Unlike idiopathic SLE, which affects women more than men, drug-induced SLE has no predilection for either sex. Clinically, drug-induced SLE may also be differentiated from idiopathic SLE by the lack of renal and central nervous system (CNS) involvement.

Procainamide's ganglion-blocking properties may lead to periperal vasodilation and systemic hypotension. Rarely, blood dyscrasia may develop; these patients may present with gingival or GI bleeding, bruising, or fever and sore throat.[18, 19, 20]


Quinidine toxicity manifests primarly through GI, neurologic and cardiovascular symptoms.  Cinchonism, a syndrome characterized by GI symptoms (abdominal cramping, nausea, vomiting, and diarrhea), tinnitus, and altered mental status may occur in both chronic and acute toxicity. Quinidine can cause immune-mediated hematalogic reactions such as rash, fever, anaphylaxis, hemolytic anemia, thrombocytopenia, and leukopenia. Rarely, quindine can be associated with a procainamide-like drug-induced SLE.

Patients on quinidine may report neuroglycopenic or adrenergic symptoms of hypoglycemia, as the drug acts on potassium channels in the pancreatic islet cells. Like procainamide and disppyramide, quinidine can cause anticholinergic symptoms such as dry mouth, visual blurring, or urinary retention. Quinidine has alpha-adrenergic antagonistic effects that may cause peripheral vasodilation, hypotension, and syncope.[21, 22]


Lidocaine toxicity predominantly involves CNS effects. Mild-to-moderate lidocaine toxicity may result in the following:

  • Drowsiness
  • Insomnia
  • Light-headedness
  • Dysphoria
  • Vision changes
  • Tinnitus
  • Dysarthria
  • Ataxia
  • Depression
  • Agitation
  • Personality changes
  • Tongue numbness
  • Nystagmus
  • Hallucinations
  • Memory difficulty
  • Paresthesias

Severe lidocaine toxicity may result in seizures or coma.


Patients may report neurotoxic adverse effects similar to those that occur with lidocaine. Patients may also report nausea and vomiting.


Flecainide has generally nonfatal extracardiac effects that are promarily CNS in nature. These include visual blurriness, nausea, dizziness, confusion, and headache. Severe CNS toxicity, such as seizures, paranoid psychosis, hallucinations, and dyarthria, may occur, especially in patients with renal failure. An adverse effect of flecainide is worsening of congestive heart failure; these patients may report increased dyspnea on exertion, lethargy, and peripheral edema.  Patients with cardiomyopathy may present in cardiac arrest from dysrhythmia. 


Patients with preexisting systolic dysfunction may report symptoms suggestive of worsening heart failure, such as dyspnea and edema. Common adverse effects include alteration in taste, blurred vision, and dizziness. GI adverse effects of nausea, vomiting, and constipation are also reported. Asthmatic patients may report worsening symptoms, owing to the weak beta-blocking effects of propafenone.  CNS adverse effects, such as dizziness, nausea, unusual taste, and blurred vision, are often dose dependent.

Propafenone may lead to agranulocytosis leading to immunosuppresion. Rarely, rash or SLE-like symptoms may occur. 


Beta-blockers are class II antidysrhythmics. Complications from these drugs are covered in Beta-Blocker Toxicity.


Amiodarone has a number of extracardiac adverse effects, involving the lungs, thyroid, liver, CNS, and skin. Rapid intravenous amiodarone infusion may cause hypotension due the solvent base in which it is dissolved, or excipients such as benzyl alcohol or polysorbate 80. Aqueous solvent bases or formulations with cyclodextrin instead of benzoyl alcohol or polysorbate 80 have been found to not cause this reaction. Rapid infusion may also cause bradyarrhythmias and asystole. Otherwise, toxicity from amiodarone is generally attributed to prolonged use.[23, 24]

Amiodarone-induced pulmonary toxicity is the adverse effect of greatest concern. Suspected mechanisms of amiodarone lung toxicity include immunologic effects and direct cytotoxicity.[25, 26]  

Pulmonary toxicity from amiodarone may manifest as pulmonary fibrosis, chronic interstitial pneumonitis, bronchiolitis obliterans, a solitary lung mass, or pleural effusion. Patients may report cough, fever, hemoptysis, malaise, dyspnea, weight loss, and occasionally pleuritis. The most worrisome presentation involves acute diffuse pneumonitis and respiratory failure resembling acute respiratory distress syndrome (ARDS), which may occur in patients with underlying lung disease and high oxygen requirements.

Other adverse effects of amiodarone include the following[27, 28] :

  • Thyroid: Symptoms suggestive of hyperthyroidism or hypothyroidism
  • Hepatotoxicity leading to cirrhosis (uncommon)
  • Dermatologic: Photosensitivity, bluish skin discoloration
  • Ophthalmologic: Vision loss from corneal deposition, optic neuropathy, or optic neuritis
  • Light-headedness from bradycardia or hypotension (rare)
  • CNS: Clumsiness, dizziness, tremulousness, sensation changes, cognitive difficulty, or sleep disturbances


Patients taking dronedarone may report nausea, diarrhea, and abdominal pain. A minority of patients may develop rash. Patients may report light-headedness or syncope related to bradycardia. Patients may report new or worsening heart failure symptoms. Dronedarone is contraindicated in patients with severe or worsening heart failure.[29]

Unlike amiodarone, dronedarone is not typically associated with thyroid, neurologic, or ocular toxicity. Rare cases of pulmonary toxicity have been reported, and patients may report increasing shortness of breath or cough.  


Patients may report palpitations, chest pain, light-headedness, fatigue, insomnia, headhche, dyspnea, or weakness. Patients with reactive airway disease may develop shortness of breath and wheezing. Sotalol may also cause GI symptoms such as  mild diarrhea, nausea, or vomiting. 


Headache occurs in a minority of patients. 


The most common adverse effects that patients report are headache, chest pain, and light-headedness.

Calcium channel blockers

Complications from these class IV drugs are covered in Calcium Channel Blocker Toxicity.


Transient adverse effects are common and include headache, flushing, chest pressure, and dyspnea. These generally resolve quickly without any intervention. 

Physical Examination

Physical examination and electrocardiography findings


Cardiotoxicity includes negative inotropic effects through its blockade of myocardial calcium channels, PR prolongation, and QTc prolongation that may progress to torsade de pointes. CNS and anticholingeric effects may include mydriasis, urinary retention, dry skin, dry mucus membranes, increased ocular pressure with worsening vision and pain in glaucoma. CNS effects may include confusion and hallucinations. Other adverse effects include signs of worsening heart failure such as increased jugular venous distention (JVD), peripheral edema, and rales.


Acute cardiotoxicity may result in any of the following:

  • Prolongation of the corrected QT (QTc) interval
  • Tachydysrhythmia
  • Bradycardia
  • Torsade de pointes
  • Left ventricular dysfunction
  • Ventricular tachycardia
  • Premature ventricular contractions
  • Atrioventricular (AV) block in patients with preexisting AV conduction abnormalities
  • Significant systemic hypotension due to vasodilation or dysrhythmia

Drug-induced lupus findings in patients on long-term therapy include  morbilliform and malar rash, joint swelling with pain and restricted range of motion, as well as respiratory symptoms related to pleuritis.

Other neurologic acute symptoms may include seizures and psychosis. An allergic response may provoke fever. Physical signs from blood dyscrasias include ecchymosis, petechiae, purpura, pharyngitis, lymphadenopathy, and fever.[30]


Cardiotoxicity causes hypotension, QRS widening, QTc prolongation, and PR prolongation.

Hematologic and immune-mediated toxicity may result in fever, bruising, rash, and respiratory symptoms.

CNS toxicity causes vision changes, seizures, lethargy, coma, and central apnea.


Lidocaine rapidly enters the CNS; a common initial sign of severe CNS toxicity is seizures. Seizures can be followed by coma and respiratory arrest. Other signs of CNS toxicity include somnolence and muscle fasciculations. Tremor may be the first sign of toxicity. Patients may become confused or show personality changes.

Cardiotoxicity may result in sinus arrest, atrioventricular block, hypotension, and cardiac arrest; prolongation of PR, QRS, and QT interval can occur in severe overdose.


CNS toxicity causes seizures, lethargy, confusion, and coma.

Cardiotoxicity can result in bradycardia, atrioventricular nodal block, torsades de pointes, ventricular fibrillation, hypotension, and cardiovascular collapse. 


CNS toxicity may present as seizures, altered mentation, and stroke-like symptoms. 

Cardiotoxicity (see image below) results in widening of QRS complexes (50% or greater increase), PR prolongation (30% or greater increase) leading to first- or second-degree heart block, QTc prolongation (15% or greater increase), bradycardia, AV block, ventricular fibrillation, and hypotension. Ventricular depolarization may be prolonged, increasing risk of torsade de pointes. 

ECG in a patient who ingested 4 of flecainide. QRS ECG in a patient who ingested 4 of flecainide. QRS = 200 milliseconds; QTc = 585 milliseconds. Used with permission from Lippincott, Williams & Wilkins (in Martindale JL, Brown DFM. Rapid Interpretation of ECGs in Emergency Medicine: A Visual Guide. Lippincott Williams and Wilkins; 2012).

Flecainide may cause ST elevation in lead V1 characteristic of Brugada syndrome[31] (and is used to assist diagnosis of patients suspected of having Brugada syndrome). A 1:1 atrioventricular conduction may occur during treatment of atrial flutter if the patient is not already on AV nodal blockers.[32, 8]


CNS toxicity results in seizures. Ataxia has been reported. 

Cardiotoxicity causes widening of the QRS complex and sinus bradycardia. The negative inotropic effect may lead to systemic hypotension and overt heart failure.[33]


Cardiac effects include QTc prolongation, PR prolongation, sinus bradycardia, ventricular dysrhythmias, torsade de pointes, AVblock, and hypotension. Torsade de pointes is an extremely uncommon complication with amiodarone, compared with other antiarrythmics that prolong the QTc interval, probably because of amiodarone's other mechanisms of action. 

Jaundice may occur with hepatotoxicity and intrahepatic cholestasis. 

Physical exam abnormalities of hyperthyroidisms or hypothyroidism may be evident. 

Rash with bluish discoloration or increased photosensitivity and sunburn may occur.

CNS toxicity may be observed on exam, with hyperrefllexia, tremor, gait ataxia, confusion, and sensory changes associated with peripheral neuropathy. Tremor and hyperreflexia may also be a manifestation of amiodarone-induced thyrotoxicosis.

Pulmonary toxicity may manifest as crackles or rales without clubbing. 


Findings in patients with adverse effects include the following:

  • Cardiac effects include bradycardia, QTc prolongation, and hypotension. Torsade de pointes has not been reported.
  • Pulmonary toxicity may mainfest crackles or rales without clubbing.
  • Liver dysfunction may result in jaundice or other signs of hepatic failure. 


Cardiac effects can include significant bradycardia, AV block, hypotension, QTc prolongation, and ventricular arrhythmias (eg, torsades de pointes). Long-term use of sotalol is associated with a 2.5% risk of torsades de pointes[34] ; consider torsades as a possible event for patients who present with a history of syncope.


Patients receiving an infusion of ibutilide may become bradycardic,  hypotensive, or develop torsade de pointes. Toxicity from overdose is not reported.


Cardiac effects include QTc prolongation and torsade de pointes, as well as ventricular fibrillation.


In addition to the transient asystole that is the treatment goal, patients may develop bradycardia, AV block, or sinus arrest. Atrial fibrillation may be induced. 

Rarely, bronchospasm may occur, especially in patients with underlying reactive airway disease. 



Differential Diagnoses



Approach Considerations

Laboratory tests

Laboratory tests for patients with antidysrhythmic toxicity vary according to the individual agent.

The role of drug concentration testing for acute toxicity in the emergency department is extremely limited. Serum concentrations of quinidine and lidocaine may be measured in the acute care setting, but treatment for presumed toxicity should be based on clinical grounds rather than serum concentrations. 

Therapeutic concentrations for quinidine are 2-6 mg/mL, and toxic concentrations are greater than 8 mg/mL. Concentrations above 14 mg/mL are associated with cause cardiac toxicity in most patients.

Tests for levels of lidocaine and its metabolite, monoethylglycinexylidide (MEGX), are available. Effective plasma concentrations are 1.5-5 mg/mL. CNS toxicity is seen with 7 mg/mL, and fatal concentrations are greater than 15 mg/mL for an adult and at least 3.8 mg/mL for a child.

Electrolyte assays, including potassium and magnesium levels, are appropriate for patients taking drugs that can prolong the corrected QT (QTc) interval.


An electrocardiogram (ECG) should be performed on every patient with suspected antidysrhythmic toxicity. Physicians should look out for features such as QRS widening and QTc prolongation. QRS widening is most likely to be present in patients taking drugs with sodium-channel blocking effects (class I antidysrhythmics, amiodarone, dronedarone). QTc prolongation can occur with any drug that delays repolarization (class IA, IC, and III drugs).

Monitoring and evaluation of individual agents


Cardiac monitoring, serial ECGs and blood pressure measurements should be performed regularly. Vital signs should be monitored to assess for excessive anticholenergic effects and any evidence of worsening heart failure or dysrhythmias. Serum mono-N-dealkyldisopyramide concentration can be measured and if it is over approximately 1 microg/mL, the dose should be decreased or discontinued. Blood glucose should be regularly monitored.


Renal function and hepatic function should be assessed and monitored throughout therapy. ECGs and blood pressure measurements should be performed regularly. Agranulocytosis and pancytopenia can occur at therapeutic doses; a complete blood cell count (CBC) with differential should be obtained regularly during the first 3 months of therapy and then periodically checked. Antineutrophil antibody (ANA) and anti-histones may be monitored for rising levels to evaluate for drug-induced systemic lupus erythematosus (SLE). Unlike drug-induced lupus, idiopathic SLE will be positive for anti-double stranded DNA antibodies and hypocomplementemia.[18, 35]


Cardiac monitoring, ECGs, and frequent vital sign reassessments are indicated. Serum creatinine should be checked and the quinidine dosage reduced if the patient has renal insufficiency. A CBC should be checked for hematologic reactions.


Lidocaine toxicity is primarily assessed clinically. Lidocaine should be administered under ECG monitoring during cardiac arrest events. If the clinician is concerned about local anesthetic toxicity, IV access and cardiac monitoring should be instituted. In severe toxicity, blood gases may be obtained.


Drug initiation should take place in a monitored hospital setting, given the potential for ventricular dysrhythmias.


Blood pressure, renal function, and hepatic function should be assessed before drug administration. Serum concentrations can be followed in patients with hepatic or renal insufficiency. Electrolytes should be monitored. 


ECG, blood pressure, and hepatic function tests should be performed at baseline. Agranulocytosis can occur, so a CBC with differential should be periodically checked.


Amiodarone toxicity is cumulative, with increased dosage and length of treatment time as the largest factors. Patients at highest risk of amiodorone toxicity include those taking 400 mg/day for longer than 2 months or 200 mg/day for 2 years. 

Patients taking amiodarone should have baseline pulmonary function tests, chest radiography, thyroid function tests, and liver function tests performed, and should have these tests repeated on a regular basis while taking the drug.

In patients presenting with pulmonary symptoms suggestive of pneumonitis, a positive gallium scan may help to differentiate amiodarone pneumonitis from other processes, such as pulmonary embolism and congestive heart failure[25] . 

Fatal hepatotoxicity from amiodarone occurs in 1-3% of patients.  Toxicity is dose and duration dependent. Liver function tests are recommended every 3-6 months.  

Patients with an implanted cardioverter-defibrillator (ICD) who have been loaded with amiodarone should have an ICD evaluation or an electrophysiology study to evaluate for  drug-device interactions, according to North American Society of Pacing and Electrophysiology (NASPE) guidelines. [36, 37]


Patients on dronedarone should have regular ECGs to look for evidence of QTc prolongation. Transaminase levels and electrolytes should periodically checked throughout treatment. Serum creatinine levels should be checked periodically. Concomitant medications that are renally cleared should be monitored for adverse reactions. 


Patients should have a baseline creatinine clearance and QTc interval measured before initiating therapy. QTc intervals should be checked regularly during long-term oral use. QTc interval greater than 450 milliseconds is a contraindication to therapy. Sotalol should be discontinued or reduced if the QTc exceeds 500 milliseconds or if there is a change in QTc interval exceeeding 15% from a baseline wide QRS (>120 ms).  


Patients should have a baseline ECG. Ibutilide is not recommended if the baseline QTc is greater than 440 milliseconds. Serum potassium and magnesium levels should be measured, and potassium and magnesium should be repleted before administering sotalol. Continued ECG monitoring should be performed during the dosing period and for at least 4-6 hours, given the risk for ventricular arrhythmias. Ibutilde should be used with cautions in patients with structurally abnormal hearts, depressed left ventricular function, or a history of ischemia or myocardial infarction, because ibutilde-induced torsade de pointes may be difficult to treat in such patients.[38, 15]


Initiation of dofetilide should be conducted under continued cardiac monitoring in a hospital setting for several days, to ensure that significant QTc prolongation does not occur and to avoid torsade de pointes. Dofetilide should not be given to patients with a creatinine clearance of less than 20 mL/min or a baseline QTc greater than 440 milliseconds. The initiation and prescription of dofetilide should be restricted to physicians who have trained in the monitoring of this medicatio,n due to its prodysrhythmic effects. 


Rhythm monitoring should be performed during administration of adenosine, ideally with a continuous 12-lead rhythm strip.



Approach Considerations

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. [39]

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.[40, 41]




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.[42]

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.[43]


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.[44]


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.[45, 46, 47]

Cardiopulmonary bypass and extracorporeal membrane oxygenation have been reported and may be reasonable if available in cases of severe toxicity refractory to supportive measures.[48]

Electrolyte management is crucial in flecainade toxicity because hyponatremia can increase toxicity. [49, 50]


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.[51]  

Gastric lavage is useful in patients with severe recent toxic ingestions.[52]



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.[53]


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.[34] 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[54] and calcium channel blocker overdose.[55, 56] Flecainide overdose has also been treated successfully with ILE.[45] This approach may be considered for amiodarone overdose, given that drug's high degree of lipophilicity and partitioning into the lipid emulsion compartment.[57]

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.



Medication Summary

Discontinuation of the precipitating drug is of paramount importance. Gastrointestinal decontamination is empirically used to minimize systemic absorption of the drug. Hemodialysis may be indicated in certain drug toxicities as well as targeted antitidotal therapies.

Antidotes, Other

Class Summary

GI decontamination with oral activated charcoal is selectively used in the emergency treatment of poisoning caused by some drugs and chemicals.

Activated charcoal (Actidose-Aqua, EZ-Char, Kerr Insta-Char)

Activated charcoal is used in emergency treatment for poisoning caused by drugs and chemicals. A network of pores adsorbs 100-1000 mg of drug per gram. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. Theoretically, by constantly bathing the GI tract with charcoal, the intestinal lumen serves as a dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into intestine.

Activated charcoal achieves its maximum effect when administered within 30 minutes after ingestion of a drug or toxin. However, decontamination with activated charcoal may be considered in any patient who presents within 4 hours after the ingestion.

Repeated doses may help to lower systemic levels of ingested compounds, especially sustained-release preparations. Activated charcoal does not dissolve in water. Supply it as an aqueous mixture or in combination with a cathartic (usually sorbitol 70%).

Electrolyte Supplements, Parenteral

Class Summary

Potassium and magnesium should be repleted in patients taking QTc-prolonging drugs. High doses of magnesium may decrease the risk of QTc prolongation during ibutilide infusions.

Calcium chloride

Calcium is given to reverse hypotension and improve cardiac conduction defects. Calcium chloride theoretically increases calcium's concentration gradient, overcoming the channel blockade and driving calcium into the cells. It moderates nerve and muscle-performance by regulating action potential excitation threshold.

Magnesium sulfate

Magnesium acts as an antidysrhythmic agent and diminishes the frequency of premature ventricular contractions (PVCs), particularly those resulting from acute ischemia. Deficiency in this electrolyte can precipitate refractory ventricular fibrillation (VF) and is associated with sudden cardiac death. Magnesium supplementation is used for treatment of torsade de pointes, known or suspected hypomagnesemia, or severe refractory VF.

Sodium bicarbonate (Neut)

Intravenous sodium bicarbonate can be life saving in patients presenting with cardiotoxicity from antidysrhythmics with sodium-channel blocking properties and QRS widening. Sodium bicarbonate can be given as 1-2 mEq/kg (typically 100 mEq) as a bolus, followed by continuous infusion if the QRS narrows after bolus infusion. A 12-lead EKG should be run while administering the sodium bicarbonate bolus to ensure that QRS narrowing isn't missed because of a delayed EKG. Serum pH should be monitored if a sodium bicarbonate infusion is used. 

Alpha/Beta-Adrenergic Agonists

Class Summary

Vasopressors are indicated for persistent hypotension not responsive to judicious fluid loading and sodium bicarbonate.

Norepinephrine (Levophed)

Norepinephrine has strong beta1- and alpha-adrenergic effects and moderate beta2 effects, which increase cardiac output, blood pressure, and heart rate, while decreasing renal perfusion and pulmonary vascular resistance

Beta1/Beta2 Adrenergic Agonists

Class Summary

These agents may be used to treat symptomatic arrhythmia.

Isoproterenol (Isuprel)

Isoproterenol is used to treat torsade de pointes if magnesium supplementation fails to treat it. It is also used to treat ventricular tachycardia or fibrillation in the setting of Brugada syndrome.

Anticonvulsants, Other

Class Summary

By increasing the action of gamma aminobenzoic acid (GABA), a major inhibitory neurotransmitter, benzodiazepines may depress all levels of the central nervous system (CNS), including the limbic system and the reticular formation.

Diazepam (Valium, Diastat)

Diazepam depresses all levels of the CNS (eg, limbic system and reticular formation), possibly by increasing the activity of GABA. It is a third-line agent for agitation or seizures because of its shorter duration of anticonvulsive effects and the accumulation of active metabolites that may prolong sedation.

Lorazepam (Ativan)

Lorazepam is the drug of choice for treatment of status epilepticus because persists in the CNS longer than diazepam. The rate of injection should not exceed 2 mg/min. This agent may be administered intramuscularly if vascular access cannot be obtained.


Midazolam is an alternative agent for termination of refractory status epilepticus. Compared with diazepam, midazolam has twice the affinity for benzodiazepine receptors; however, because it is water soluble, midazolam takes approximately 3 times longer than diazepam to achieve peak electroencephalographic effects. Thus, the clinician must wait 2-3 minutes to fully evaluate sedative effects before initiating a procedure or repeating the dose. This agent may be administered intramuscularly if vascular access cannot be obtained.