DESCRIPTION

The class IB antidysrhythmic agents include lidocaine, xylocaine, mexiletine, and tocainide.

FORMS AND USES

• Lidocaine HCL [EMLA cream (lidocaine 2.5%), viscous gel (2%-4% lidocaine)] is used as a topical anesthetic.
• Xylocaine for injection (50- or 100-mg prefilled syringes and ampules) is used for ventricular dysrhythmia as well as local anesthesia.
• Mexiletine HCL (Mexitil in 150-, 200-, or 250-mg capsules) is used for the treatment of life-threatening ventricular dysrhythmia. Dosage is 200 to 400 mg orally every 8 hours.
• Tocainide HCL (Tonocard in 100- or 600-mg tablets) is also used for the treatment of life-threatening ventricular dysrhythmia. Typical adult dosage is 1,200 to 1,800 mg/day in divided doses.
• Phenytoin HCL (Dilantin) is also used (see SECTION IV, Phenytoin chapter, for details).

TOXIC DOSE

Toxicity has occurred after ingestion of 5 to 10 mg/kg of lidocaine. The dose for tissue infiltration should not exceed 5 mg/kg (7 mg/kg for a lidocaine-epinephrine combination product).

PATHOPHYSIOLOGY

• Antidysrhythmic class IB agents depress phase IV depolarization of the cardiac action potential by producing a blockade of the fast inward sodium channel. This reduces spontaneous pacemaker activity and slows propagation of impulse conduction through myocardial tissue.
• These agents have a narrow therapeutic range, and toxicity may develop with therapeutic doses. Conduction delays and asystole may occur after a large intravenous dose of lidocaine.

EPIDEMIOLOGY

• Poisoning is uncommon.
• Toxic effects following an overdose are typically moderate, with death occurring in patients who deteriorate before reaching medical care or who receive a massive acute overdose.

CAUSES

• Toxicity from parenteral medication is often iatrogenic.
• An overdose from oral medications is usually an intentional ingestion
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

RISK FACTORS

A preexisting cardiac conduction defect predisposes the patient to adverse effects even at therapeutic doses.

DRUG AND DISEASE INTERACTIONS

• Theophylline enhances the toxicity of mexiletine.
• All antidysrhythmic class IB agents have an additive effect when combined with negative inotropic or chronotropic medications.

PREGNANCY AND LACTATION

All agents. US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in animals or women.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of CNS depression, seizure, and ECG conduction abnormalities include class I antidysrhythmics, antihistamines, cocaine, beta-receptors or calcium channel blockers, quinine, chloroquine, digoxin, phenothiazine, and cyclic antidepressants, among others.
• Other causes of CNS depression and seizure include head trauma, elevated intracranial pressure, and electrolyte abnormalities.

SIGNS AND SYMPTOMS

Restlessness is often the first sign of toxicity. CNS effects typically develop before dysrhythmia. Toxicity of intravenous lidocaine is immediate.

Vital Signs

Bradycardia and hypotension are common after serious ingestion.

HEENT

• Diplopia and nystagmus have been reported with tocainide.
• Miosis and tinnitus have been reported with mexiletine and lidocaine at high doses.

Cardiovascular

Various dysrhythmias ranging from nodal bradycardia to third-degree atrioventricular (AV) block and asystole may occur.

Pulmonary

• Apnea and respiratory depression occur in a serious overdose.
• A diagnostic ECG effect has not been defined. Antidysrhythmic class IB agents do not typically affect the ECG in therapeutic doses, although the QT interval may be prolonged.

Gastrointestinal

Nausea, vomiting, and abdominal pain are common.

Hematologic

Methemoglobinemia may occur in lidocaine toxicity.

Neurologic

Neurologic effects occur early, ranging from restlessness, dizziness, and confusion to irritability, frank psychosis, seizure, and coma.

LABORATORY PROCEDURES AND TESTS

Essential Tests

• ECG with continuous monitoring is used to assess evidence of conduction delay, enhanced automaticity, or QTc prolongation. Should any of these be present, prompt aggressive treatment is needed.
• Serum levels may be available, but treatment should not be delayed for blood levels to confirm the diagnosis.
• Serum electrolytes, calcium, magnesium, BUN, creatinine, and glucose are measured to assess other causes of dysrhythmias.

Recommended Tests

• Arterial blood gas. Circumoral paresthesia and subtle mental status changes may be misidentified as anxiety or hyperventilation.
• Additional drug assays (lithium, opiates) should be performed as needed to assess other causes of mental status depression, seizures, or hypotension.
• Serum acetaminophen and aspirin levels should be measured in an overdose setting to detect occult ingestion.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Hematologic
  • Neurologic
• LABORATORY PROCEDURES AND TESTS
  • Essential Tests
  • Recommended Tests

• Treatment is focused on aggressive airway management, seizure control, and treatment of dysrhythmia.
• The dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Altered mental status, bradycardia, or other severe effects are present.
• Toxic effects are not consistent with class IB antidysrhythmic poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Toxic effects are present.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted for patients with apparent toxic effects of class IB antidysrhythmic agents.

DECONTAMINATION

Out of Hospital

Do not induce emesis; coma or seizures may develop abruptly.

In Hospital

• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestion presenting within 1 hour of ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours. However, this is not indicated for parenteral lidocaine exposure.

ANTIDOTES

There is no specific antidote for class IB antidysrhythmic agent poisoning.

ADJUNCTIVE TREATMENT

Bradydysrhythmia

• Atropine and isoproterenol are recommended, but usually ineffective. Early use of a pacemaker is recommended.
• Emergency cardiopulmonary bypass should be considered in life-threatening lidocaine toxicity because it can allow the liver to continue to metabolize lidocaine. Nontoxic levels may be reached within hours.

Ventricular Dysrhythmias

For stable patients, begin with drug therapy as described below. For unstable patients, use defibrillation followed by pharmacologic therapy.

• Sodium Bicarbonate. Administer NaHCO₃ 1 to 2 mEq/kg in an intravenous bolus and repeat as needed to suppress dysrhythmia, but do not exceed pH of 7.55. Simultaneous hyperventilation and bicarbonate therapy must be administered cautiously because it may cause severe alkalemia.
• Seizures should be controlled concurrently.
• Cardiac bypass may be used to maintain perfusion and allow continued quinidine or lidocaine metabolism in patients with refractory dysrhythmia or hypotension.
• Avoid bretylium because beta-blocking effects may worsen hypotension. Avoid other class I antidysrhythmic agents because they may worsen the dysrhythmias.

Torsade de Pointes

• Correct electrolyte abnormalities if present.
• Avoid quinidine, disopyramide, procainamide, amiodarone, and bretylium, which also prolong the QT interval.
• Magnesium sulfate (MgSO₄)
  • Adult dose is 1 to 2 g intravenous push, may be repeated in 10 to 15 minutes. Begin intravenous infusion at 2 to 10 mg/min, titrate upward to maintain antidysrhythmic effect.
  • Pediatric dose is 25 to 50 mg/kg intravenously over 5 minutes.
• Isoproterenol
  • Adult dose 2 to 4 µg/ml solution is infused intravenously at an initial rate of 0.5 to 1.0 µg/kg/min, titrated upward to effect.
  • Pediatric dose is 0.1 µg/kg/min intravenous infusion, titrated to effect.
  • If unresponsive, overdrive pacing may be used.
• Hypotension. The primary treatment is correction of the dysrhythmia. Also administer 10 to 20 ml/kg 0.9 saline, place patient in the Trendelenburg position, and administer a vasopressor, if needed. Dopamine is preferred, and norepinephrine is added for refractory hypotension.
• Seizures
  • A patent airway must be ensured.
  • A benzodiazepine is administered for initial control. If seizures persist or recur, another anticonvulsant such as phenobarbital may be added.

Cardiac Pacing

Cardiac pacing may be useful in patients with bradycardia or AV block who are not responsive to other measures.

• Not recommended. Hemodialysis, hemofiltration, hemoperfusion, forced diuresis, and urinary acidification are not recommended.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Bradydysrhythmia
  • Ventricular Dysrhythmias
  • Torsade de Pointes
  • Cardiac Pacing

PATIENT MONITORING

• Respiratory and cardiac function should be monitored continuously.
• Serial levels of mexiletine and tocainide should be monitored to assure they are decreasing.

EXPECTED COURSE AND PROGNOSIS

• The patient usually recovers unless sequelae of hypoxia intercede.
• Survival is expected if the patient receives appropriate aggressive care before anoxic injury intercedes.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Discharge asymptomatic patients after gastrointestinal decontamination, a 6-hour observation period, and psychiatric evaluation, if needed.
• From the hospital. Discharge patients after toxic effects have resolved and after psychiatric evaluation, if needed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

• Failure to recognize subtle changes in mental status or neurological examination before seizures develop.
• An ECG alone should not be used to exclude antidysrhythmic class IB toxicity.

Poisoning by other CNS depressants and anesthetics: surface (topical) and infiltration anesthetics.

See Also: SECTION II, Hypotension and Seizure chapters; and SECTION III, Local Anesthetics and Phenytoin chapters.

RECOMMENDED READING

Brown DL, Skiendzielewski JJ. Lidocaine toxicity. Ann Emerg Med 1980;9:12;627-629.

Hruby K, Missliwetz J. Poisoning with oral antiarrhythmic drugs. Int J Clin Pharmacol Ther Toxicol 1985;23:253-257.

Author: Gerald F. O'Malley

Reviewer: Katherine M. Hurlbut