DESCRIPTION

This discussion covers abnormal ventricular rhythms or conductions arising from toxic causes.

PATHOPHYSIOLOGY

Ventricular dysrhythmias caused by toxic agents may involve several mechanisms.

• Myocardial ischemia may be due to vessel spasm, hypotension or hypoxia; hypoxia can be caused by direct lung injury, alteration of hemoglobin, or hypoventilation.
• Electrolyte abnormalities, especially hyperkalemia, hypocalcemia, or hypomagnesemia, can cause ventricular dysrhythmias.
• Blockade of ion channels in the myocardium, particularly sodium or calcium channels, may result in ventricular dysrhythmias.

RISK FACTORS

Underlying cardiovascular disease may predispose to development of dysrhythmias.

Section Outline:

• DESCRIPTION
• PATHOPHYSIOLOGY
• RISK FACTORS

DIFFERENTIAL DIAGNOSIS

Further information on each poison is available in SECTION IV, Chemical and Biological Agents.

Toxicologic Causes

Associated findings with ventricular dysrhythmias may help confirm the identity of the poison involved.

• Tricyclic antidepressants (TCAs)
  • Dysrhythmia is usually heralded by a QRS complex of 100 msec or more and altered mental status.
  • Additional findings may include seizure, hypotension, and presence of an R wave in ECG lead aVR.
  • Phenothiazines produce similar effects.
• Cocaine, amphetamines, and other sympathomimetic agents (ephedrine, phenylpropanolamine, beta-₂ receptor agonists) present with sinus tachycardia or ventricular tachydysrhythmias and are often associated with hypertension, hyperthermia, agitation, delirium, seizures, and rhabdomyolysis.
• Antihistamine and anticholinergic agents (diphenhydramine, scopolamine, jimsonweed weed, hydroxyzine, phenothiazine, dramamine, etc.) present with sinus tachycardia or ventricular dysrhythmias and may be indicated by flushing, dilated pupils, diminished bowel sounds, hyperthermia, hallucination, agitation, and delirium. Widening of the QRS complex and prolongation of the QT interval occur in a severe overdose.
• Theophylline is associated with tremor, vomiting, seizures, dysrhythmias, hypokalemia, mild metabolic acidosis, and preexisting diagnosis of chronic obstructive pulmonary disease. Sinus tachycardia and atrial and ventricular ectopy are most common. Ventricular tachycardia is rare, although ventricular fibrillation may occur following a single massive overdose.
• Type Ia antiarrhythmic agents (quinidine, procainamide, disopyramide) all cause QT interval prolongation.
• Digitalis may produce visual complaints, heart block, vomiting, hyperkalemia (acute), or hypokalemia (chronic intoxication). Premature ventricular contractions are the most common digitalis-induced dysrhythmias, although any dysrhythmia, even tachydysrhythmias, may result from digitalis toxicity.
• Monoamine oxidase (MAO) inhibitors may cause hyperthermia, hypertension, muscle rigidity and altered mental status. Ventricular tachydysrhythmias are often the presenting cardiovascular effect of MAO inhibitor ingestion.
• Carbamazepine is associated with coma, hyponatremia, and nystagmus. In a large overdose, carbamazepine may produce cardiac effects similar to TCAs.
• Organophosphate or carbamate pesticides also may cause vomiting, diarrhea, salivation, lacrimation, urination, bronchorrhea, small pupils, and sweating. Classically, organophosphates has been reported to cause bradydys-rhythmias, but in reality, sinus tachycardia is often the presenting dysrhythmia.
• Substances that produce methemoglobinemia often cause cyanosis.
• Thyroid hormones generally cause supraventricular tachycardia; ventricular dysrhythmia may complicate severe cases. They are associated with history of thyroid disease, tremor, and fever.

NONTOXICOLOGIC CAUSES

Nontoxicologic causes include primarily coronary artery disease, congenital cardiac abnormalities, intracranial bleed, hypoglycemia, electrolyte abnormalities, or hypoxia.

SIGNS AND SYMPTOMS

• Patients may develop weakness, dizziness, chest pain, palpitations, or any symptom of hypoxia.
• Syncope, seizure, or cardiac arrest may occur precipitously in severe cases; syncope should be considered a sign of ventricular dysrhythmia until proven otherwise.

Vital Signs

Hypertension may indicate sympathomimetic toxicity or withdrawal from alcohol, sedative-hypnotic agents, or MAO inhibitors.

HEENT

Dilated pupils suggest anticholinergic or sympathomimetic toxicity.

Dermatologic

• Flushed, dry skin suggests an anticholinergic agent.
• Pale, sweaty skin may be associated with sympathomimetic drugs, cholinergic agents, or hypotension.
• Cyanosis suggests hypoxia or methemoglobinemia.

Cardiovascular

• QRS widening prior to ventricular tachycardia suggests poisoning by type 1 antiarrhythmics, TCAs, phenothiazine, antihistamine, chloroquine, quinine, sotalol and several others.
• "Slow VT" suggests digitalis or calcium channel blocker toxicity.

Pulmonary

Cholinergic agonists may produce bronchorrhea and wheezing.

Gastrointestinal

• Vomiting is commonly associated with digitalis, iron, salicylate, or theophylline intoxication.
• Diminished bowel sounds suggest an anticholinergic agent.

Renal

Urinary retention suggests an anticholinergic agent.

Fluids and Electrolytes

• Hypokalemia suggests a beta-receptor agonist or theophylline.
• Hyperkalemia may indicate acute digitalis intoxication.

Neurologic

• Hallucinations and delirium suggest an anticholinergic agent or abuse of stimulants or hallucinogens.
• Anxiety, tremor, and seizures suggest theophylline or withdrawal from alcohol or sedative-hypnotic drugs.
• Coma and seizure suggest TCAs or type 1 antidysrhythmic drugs.
• CNS depression or coma, nystagmus, ataxia, diminished bowel sounds, or hyponatremia suggest carbamazepine.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• ECG and continuous cardiac monitoring should be performed to assess conduction abnormalities and evaluate underlying cardiac disease or ischemia.
• Arterial blood gases should be obtained in patients with clinical effects or who are receiving bicarbonate therapy.
• Serum electrolytes, glucose, BUN, creatinine, calcium, magnesium, and phosphorus levels should be obtained to evaluate for other causes of dysrhythmia.

Recommended Tests

• Serum salicylate, methanol, ethylene glycol, iron, lactate, and carboxyhemoglobin levels should be obtained in cases of metabolic acidosis of unknown etiology with tachycardia.
• Serum acetaminophen and aspirin levels should be obtained in overdose settings to detect an occult overdose.
• Urine toxicology screen should be performed in patients with dysrhythmia of unknown cause.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
  • Toxicologic Causes
• NONTOXICOLOGIC CAUSES
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Fluids and Electrolytes
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Supportive care with appropriate airway management is vital; many patients require endotracheal intubation. Specific treatment should be initiated while supportive care continues.
• The dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

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

• The cause of dysrhythmia is unclear.
• Coingestant, drug interaction, or underlying disease presents unusual problems.

Admission Considerations

All patients with new ventricular dysrhythmia should be admitted to an intensive care unit.

DECONTAMINATION

• Emesis should not be induced because coma or seizures may develop abruptly.
• Gastric lavage should be performed in pediatric (tube size 16-28 French) and 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.

ANTIDOTES

• There is no antidote specific to ventricular dysrhythmias.
• Antidotes to specific toxins should be used as indicated by evaluation (see SECTIONS III and IV).

ADJUNCTIVE TREATMENT

Hypoxia and Electrolyte Abnormalities

Hypoxia and electrolyte abnormalities should be corrected as clinically indicated.

Bradydysrhythmia

Standard agents, including atropine and isoproterenol, are usually ineffective; early use of specific antidotes followed by a pacemaker is recommended.

Ventricular Dysrhythmias

For stable patients, drug therapy may be begun without delay; for unstable patients, the Advanced Cardiac Life Support algorithm should be used.

Sodium Bicarbonate

• Indication: Widening of the QRS complex to more than 0.16 seconds. Some authorities recommend treatment at the QRS complex to more than 0.12 seconds.
• Dosage: A dose of 1 to 2 mEq/kg should be administered in an intravenous bolus and repeated as needed but should not raise the arterial pH above 7.55.
• Simultaneous hyperventilation and bicarbonate therapy must be undertaken cautiously because they may cause severe alkalemia.

Lidocaine

• Indication: Frequent premature ventricular contractions or ventricular tachycardia.
• Adult dose is 1.0 to 1.5 mg/kg in an intravenous push, and infusion should be titrated from 1 to 4 mg/min to maintain suppression; doses of 0.50 to 0.75 mg/kg boluses may be repeated and maintenance infusions increased every 5 to 10 minutes until ventricular tachycardia resolves or a total of 3 mg/kg has been given.
• Pediatric dose is 1 mg/kg intravenously, intraosseously, or endotracheally, and the same dose may be repeated in 10 to 15 minutes; if a second dose is required, infusion should be started at 20 to 50 µg/kg/min.
• Lidocaine dosage should be reduced in patients with hepatic insufficiency, congestive heart failure, or cardiogenic shock and in patients over 70 years of age.

Phenytoin or Fosphenytoin

• Indication: Ventricular dysrhythmia unresponsive to other agents.
• Dosage: Phenytoin loading dose for adults and children is 15 to 20 mg/kg intravenously, and the rate of infusion should not exceed 50 mg/min (adults) or 1.5 mg/kg/min (children); maintenance dose for adults is 100 mg every 6 to 8 hours, and ECG and blood pressure should be monitored during infusion, which should be stopped if dysrhythmia or hypotension occurs.
• Fosphenytoin loading dose is 15 to 20 mg of phenytoin equivalents/kg, given at a rate of 100 to 150 mg phenytoin equivalents/min.
• Bretylium should be avoided, because alpha-blocking effects may worsen hypotension; other class IA antiarrhythmic agents should also be avoided because they may worsen dysrhythmias.

Torsade de pointes

• Electrolyte abnormalities, if present, should be corrected first.
• Quinidine, disopyramide, procainamide, amiodarone, and bretylium should be avoided because they prolong the QT interval.
• In adults, 1 to 2 g of magnesium sulfate should be administered in an intravenous push, and the dose may be repeated in 10 to 15 minutes; intravenous infusion should begin at 2 to 10 mg/min and titrated to antidysrhythmic effect.
• In children, 25 to 50 mg/kg of magnesium sulfate should be administered intravenously over 5 minutes.
• Isoproterenol should be administered 2 to 4 µg/ml, initially 0.5 to 1.0 µg/min, and titrated to effect; in children, 0.1 µg/kg/min may be administered and titrated to effect.
• Overdrive pacing may be used for unresponsive patients.

Hypotension

The primary treatment of hypotension is correction of the dysrhythmia; in addition, 10 to 20 ml/kg of 0.9% saline should be administered, the patient placed in the Trendelenburg position, and a vasopressor administered if needed.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Hypoxia and Electrolyte Abnormalities
  • Bradydysrhythmia
  • Ventricular Dysrhythmias
  • Torsade de pointes
  • Hypotension

Respiratory and cardiac monitoring should be performed continuously in an intensive care setting.

The airway must be managed aggressively; many toxic deaths are due to hypoxic injury or aspiration.

Other specified cardiac dysrhythmias: other.

See Also: SECTION II, Hypertension and Seizures chapters; and SECTION IV, specific toxic agents.

RECOMMENDED READING

Hessler R. Cardiovascular principles. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Richard C. Dart

Reviewer: Katherine M. Hurlbut