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.
Electrocardiography
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
Disopyramide
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.
Procainamide
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]
Quinidine
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
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.
Mexiletine
Drug initiation should take place in a monitored hospital setting, given the potential for ventricular dysrhythmias.
Flecainide
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.
Propafenone
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
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]
Dronedarone
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.
Sotalol
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).
Ibutilide
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]
Dofetilide
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.
Adenosine
Rhythm monitoring should be performed during administration of adenosine, ideally with a continuous 12-lead rhythm strip.
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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).
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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.
