Tricyclic Antidepressant Toxicity in Pediatrics Workup

The following studies are indicated in cyclic antidepressant (CA) poisoning:

• Routine monitoring: CBC count, electrolyte levels (with determination of anion gap), urinalysis (UA), and urinary chorionic gonadotropin (UCG) levels should be routinely monitored in all patients with potential overdose.
• ABG: An arterial or venous blood sample should be sent to assess plasma pH. Cyclic antidepressant toxicity usually results in mixed acidosis due to respiratory depression coupled with hypotension caused by both myocardial depression and peripheral vasodilation, thus resulting in increased lactate production. Acidemia decreases protein binding and increases plasma levels of free drug. Therefore, correction of serum pH is a primary target of therapy in cyclic antidepressant overdose.
• Serum potassium level: Hypokalemia frequently occurs because of increased stimulation of catecholamine receptors due to blockage of norepinephrine reuptake. In one series, 9% of patients with tricyclic antidepressant (TCA) overdose had serum potassium levels of less than 3.
• Renal function tests: Cyclic antidepressant metabolites are excreted by the kidneys after hepatic metabolism by the cytochrome P450 system. Some of these metabolites are pharmacologically active, and impaired renal function may prolong or exacerbate toxicity.
• Toxicology screen: Because of the ubiquity of cyclic antidepressants and the lack of acute symptoms associated with cyclic antidepressant toxicity, serum acetaminophen levels should be routinely checked. A urine toxicology screen and screening for other potential co-ingestants (eg, ethanol, acetylsalicylic acid [ASA]) may be performed if indicated based on the clinical picture.
• Serum cyclic antidepressant level

  • Serum cyclic antidepressant levels are not readily available and not likely to be helpful in the immediate treatment of the patient with cyclic antidepressant poisoning. levels may be used to confirm suspected poisoning or give a rough estimate of overdose. However, levels do not correlate with toxic effects. This is due to the highly lipophilic nature of cyclic antidepressants and high degree of protein binding. A large volume of distribution means that tissue levels of cyclic antidepressant are often much higher than serum levels of free drug.
  • A recent meta-analysis of prognostic indicators to predict seizures, arrhythmias, and death in cyclic antidepressant overdose pooled data from 18 studies and found that the sensitivity and specificity of serum cyclic antidepressant concentration to predict ventricular arrhythmias were 0.78 (95% confidence interval [CI], 0.56-0.9) and 0.57 (95% CI, 0.46-0.67), respectively.^[7] The sensitivity and specificity of cyclic antidepressant concentration to predict death were 0.76 (95% CI, 0.49-0.91) and 0.6 (95% CI, 0.47-0.72), respectively.

Chest radiography should be performed if a history or suspicion of aspiration is noted or to rule out other causes of fever, hypotension, or respiratory failure.

Neuroimaging should also be considered for patients with altered mental status, especially if the history is unclear or if trauma is a potential comorbid contributor.

ECG is useful as both a screening tool for cyclic antidepressant exposure and as a prognostic indicator in cyclic antidepressant poisoning.^[8] See the image below.

The most common ECG finding in cyclic antidepressant poisoning is sinus tachycardia, usually due to peripheral anticholinergic effects. Other ECG changes that should be sought include prolongation of the PR, QRS, and QT intervals; atrioventricular (AV) blocks; ventricular ectopy; nonspecific ST-T changes; terminal 40-millisecond right-axis deviation of the QRS in the frontal plane; and the Brugada pattern, including right bundle branch block (RBBB) and a downsloping ST segment elevation in leads V₁ -V₃.

Cyclic antidepressants block fast sodium channels in the myocardium and slow phase zero depolarization of the action potential. Ventricular depolarization is delayed, which leads to a prolonged QRS interval. QRS interval is evaluated best using the limb leads. Widening of the QRS complex is associated with the development of seizures and arrhythmias, and QRS duration in the limb leads can be used to assess the severity of cyclic antidepressant toxicity. Patients with a QRS of less than 100 milliseconds are unlikely to develop seizures and arrhythmias. When the QRS is more than 100 milliseconds, patients have a 34% chance of seizure and a 14% chance of serious arrhythmia. QRS complexes of more than 160 milliseconds have a 50% chance of developing ventricular arrhythmias.

Cyclic antidepressants affect the right fascicle of the heart. The reason is unknown, but the effect can be observed as an exaggerated height of the R wave in lead aVR. A large R wave in lead aVR is a highly sensitive screening tool for cyclic antidepressant exposure. In addition, the amplitude of this R wave has been associated with increased risk of toxic effects. Data suggest that the finding of a large R wave in lead aVR may be even more predictive of seizure and arrhythmia than prolongation of the QRS complex. Liebelt et al found that an R wave of more than 3 mm in lead aVR was 81% sensitive and 73% specific for the development of seizures and arrhythmias.^[9]

Gastric lavage

• This may be indicated in cases in which a potentially significant ingestion is known to have occurred within 1 hour of presentation. In a study of 592 patients with TCA poisoning, Kulig et al showed that gastric lavage improved clinical outcome only when performed within 1 hour of ingestion.^[10] No evidence suggests that gastric lavage reduces morbidity and mortality if instituted outside of this time frame.

Tracheal intubation

• Clinical deterioration of symptomatic patients should be anticipated, and early intubation should be considered in these patients.
• Patients should be intubated prior to gastric lavage.
• Patients who are obtunded or comatose should be intubated for airway protection.
• Elective intubation should be considered for symptomatic patients with poor cardiopulmonary reserve who may not be able to tolerate large fluid loads induced by fluid and sodium bicarbonate therapy. Early intubation with mild hyperventilation may be used to help alkalinize the serum in these patients.