Recognize tricyclic antidepressant (TCA) toxicity and manage itaggressively

Recognize tricyclic antidepressant (TCA) toxicity and manage itaggressively: Excerpt from Avoiding Common Pediatric Errors

Author: Heidi Herrera, MD

What to Do - Interpret the Data

Although selective serotonin reuptake inhibitors are more popular, TCAs are still commonly prescribed in the treatment of enuresis, obsessive- compulsive disorder, and attention-deficit-hyperactivity disorders in children. These drugs are well-absorbed orally and are metabolized by the liver. TCA toxicity occurs by the following mechanisms: inhibiting norepinephrine and serotonin reuptake at the nerve terminals, creating anticholinergic blockade, directing β-adrenergic blockage, and blocking the cardiac myocytes fast sodium channels. The latter mechanism is a hallmark of TCA toxicity because it slows down phase zero of the action potential depolarization, and causes a widened QRS complex on the electrocardiogram (EKG).

Exposure to TCA dosages >5 mg/kg tend to be symptomatic and >15 mg/kg lethal. Early toxicity may present with signs and symptoms of anticholinergictoxidromes and central nervoussystem (CNS)involvement. The former include mydriasis, flushing, dry mouth, urinary incontinence, diminished bowel activity, hyperthermia, tachycardia; and the latter demonstrates mental status changes, confusion, hallucinations, and delirium. Mortality is attributed to cardiovascular collapse and CNS toxicity, including seizure and coma. CNS toxicity can be attributed partially to inhibition of the chloride ionophore on the . -aminobutyric acid channel complex. In general, seizures areusuallygeneralizedandself-limitedinnature.Signsofsignificanttoxicity can be expected within 6 hours of ingestion.

EKG findings can help to confirm TCA toxicity in the pediatric population. Signs include sinus tachycardia, ventricular dysrhythmias, heart block, widening QRS and QTc intervals, and an R wave >3 mm in lead aVR. A QRS duration of >100 ms is a marker of toxicity, including hypotension, coma, and airway instability.

The management of TCA toxicity includes aggressive airway protection and hemodynamic support. Patients should be placed on a continuous cardiac monitor, with adequate intravenous access, and supplemental oxygen. For neurologic deterioration with mental status changes, patients should be intubated and mechanically ventilated. Seizures can be treated with benzodiazepines. Barbiturates should be avoided due to potential hypotension. Phenytoin is not recommended for seizure control because it induces ventricular dysrhythmias in animal models. For TCA-induced cardiotoxity, widening QRS complex >100 ms, ventricular dysrhythmias, and hypotension, the first line of therapy is alkalinization with sodium bicarbonate. Starting with an IV bolus dose of 1 to 2 mEq/kg in children is appropriate, with a goal of keeping serum pH >7.5. The patient should also be monitored for hypokalemia. Antidysrhythmic medications, classes IA and IC, are contraindicated for potential of TCA-induced cardiotoxicity. Dopamine and norepinephrine may be used to overcome the β-blockadeinduced hypotension. Physostigmine is contraindicated because it leads to seizures and dysrhythmias.

In general, patients with accidental ingestion of TCAs who are asymptomatic may be observed in the emergency department for 6 hours after ingestion. If no evidence of toxicity is observed, the child may be discharged home. If symptomatic, the patient should be appropriately assessed and treated as discussed above.

Suggested Readings

Henry K, Harris CR. Deadly ingestions. Pediatr Clin North Am. 2006;53:293–315.
Michael JB, Sztajnkrycer MD. Deadly pediatric poisons: nine common agents that kill at low doses. Emerg Med Clin North Am. 2004;22:1019–1050.

Book Source Details

• Book Title: Avoiding Common Pediatric Errors
• Author(s): Anthony D Slonim MD, DrPH; Lisa Marcucci MD
• Year of Publication: 2008
• Copyright Details: Avoiding Common Pediatric Errors, Copyright © 2008 Lippincott Williams & Wilkins.

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: Avoiding Common Pediatric Errors Authors: Anthony D Slonim MD, DrPH; Lisa Marcucci MD Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7489-6

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