Tricyclic Antidepressant Toxicity in Pediatrics Treatment & Management

As always, the first priority in patients with cyclic antidepressant (CA) poisoning is to assess and treat any abnormalities in ABCs. Good supportive care is the mainstay of treatment in any overdose.

• Early intubation for patients with significant signs of toxicity, including seizures and CNS depression, is prudent. Patients who are obtunded and those with impending respiratory failure should clearly be intubated for airway protection and ventilatory support.
• Intravenous fluids should be started for patients who are hypotensive.
• Cardiac monitoring should be instituted as soon as possible because of the risk of dysrhythmias in patients with cardiovascular toxicity.
• Seizures should be treated with benzodiazepines.
• If the patient is symptomatic, a Foley catheter should be placed to relieve urinary obstruction due to anticholinergic effects and to monitor the adequacy of fluid resuscitation.
• The patient should be examined for signs and symptoms of cyclic antidepressant toxicity, and ECG should be performed early to look for a terminal R wave in lead aVR, which is a sign of cyclic antidepressant drug effect that is not necessarily indicative of toxicity, and for prolongation of the QRS and QT intervals, which is more ominous and is possibly indicative of toxin-induced sodium channel blockade.
• Symptoms of cyclic antidepressant toxicity generally present within 2 hours of ingestion. Seizures and arrhythmias are most likely to occur in the first 6 hours after ingestion. All patients with suspected cyclic antidepressant ingestion should undergo cardiac monitoring for a minimum of 6-8 hours. Monitoring should continue in symptomatic patients until the ECG findings have been normal for 24 hours.
• Asymptomatic patients should be screened for suicidal intent and admitted to a psychiatric facility as appropriate after an observation period of at least 8 hours.
• Decontamination measures include the following:

  • Syrup of ipecac is contraindicated because of the high risk of aspiration if patients become symptomatic during emesis. Patients with exposures large enough to cause symptoms may have acute alterations in mental status due to either direct CNS effects (drowsiness, delirium, seizure) or hemodynamic instability.
  • Consider gastric lavage if the patient has a known or suspected significant ingestion that occurred within 1 hour of presentation. If a lavage is to be performed, the patient should first be sedated and intubated for airway protection. A dose of charcoal should be administered via the orogastric tube prior to lavage with small aliquots of water. The administration of charcoal before lavage is advised because the lavage procedure itself may propel some amount of the ingested dose past the pylorus and into the small intestine, and this bolus is preferably premixed with an adsorbing substance.
  • Regardless of the decision to lavage, 1 g/kg of activated charcoal should be administered as soon as possible if the patient's airway protective reflexes are intact. Multidose charcoal may enhance elimination and should be considered. Charcoal should be withheld in patients who are obtunded or seizing because the risk of aspiration may outweigh the benefits of charcoal.
  • Because of the large volume of distribution and high protein binding of cyclic antidepressants, hemodialysis and hemoperfusion are not effective in enhancing drug removal.
  • Tricyclic-specific fragment antigen–binding (FAB) fragments have been developed and may eventually play a role in the decontamination of patients with cyclic antidepressant poisoning. The FAB fragments have been shown to reverse cardiotoxicity in some animal studies, and a small preliminary study in humans demonstrated no significant side effects and some clinical improvement in patients with severe cyclic antidepressant poisoning.^[11]
• Hypotension should be initially treated with intravenous fluid boluses. Refractory hypotension should be treated with pressors. Agents with alpha-adrenergic effects should be chosen. Dopamine is not usually effective in these patients because its mechanism of action partially depends on the release of endogenous norepinephrine. Cyclic antidepressants block reuptake of norepinephrine, and stores may be depleted in overdose. Animal studies have suggested that epinephrine may cause fewer arrhythmias than norepinephrine in this setting.
• Treatment of cardiac arrhythmias is as follows:

  • Cardiac arrhythmias should be treated according to the hemodynamic stability of the patient. Correction of hypoxia, hypotension and acidosis should be the first-line approach to conduction abnormalities
  • If antiarrhythmics are needed, class IA, class IC, class II, and class III drugs should be avoided. Like cyclic antidepressants, class IA and IC drugs block sodium channels and prolong depolarization and, therefore, may exacerbate their effects on the myocardium. Beta-blockers are likely to further depress myocardial contractility and cause worsening hypotension. Class III drugs prolong the QT interval and may increase the risk of a malignant ventricular arrhythmia.
  • However, class IB antiarrhythmics can increase the rate of phase zero depolarization, and phenytoin has been reported to correct conduction defects in at least one small series of patients. Several case reports of the use of magnesium and glucagons have suggested that these agents may correct ventricular arrhythmias in patients with severe cyclic antidepressant toxicity.
• Sodium bicarbonate therapy

  • Serum alkalinization with sodium bicarbonate is the mainstay of therapy in cyclic antidepressant overdose. Alkalinization of the serum to a pH level of 7.45-7.55 increases protein binding and has been shown to decrease the QRS interval, stabilize arrhythmias, and increase blood pressure in patients with tricyclic antidepressant (TCA) poisoning.
  • Patients who cannot tolerate the fluid load associated with sodium bicarbonate therapy (eg, patients with severe congestive heart failure [CHF] or renal failure) may require intubation and hyperventilation in order to achieve serum alkalinization.
  • Sodium bicarbonate may also be beneficial in treating cyclic antidepressant overdose because of the high sodium load. Animal studies and some human case reports of treatment with hypertonic saline (without serum alkalinization) have shown similar effects on myocardial conduction parameters.^[12] Therapy with hypertonic saline should be strongly considered in patients who are already alkalemic and in those who cannot tolerate the large volume load associated with intravenous bicarbonate administration.
  • Blood gases should be monitored for the development of acidosis. Sodium bicarbonate should be administered if the patient has a pH level of less than 7.1, QRS interval of more than 100 milliseconds, arrhythmias, or hypotension.
  • Bicarbonate should be administered as an initial bolus of 1-2 mEq/kg, followed by an infusion titrated to a QRS width of 100 milliseconds.
  • The serum pH should be closely monitored and should not be allowed to exceed 7.55. Serum potassium should also be closely monitored for the development of hypokalemia.
  • ECG should be monitored for the desired effect of QRS narrowing during and immediately after bolus therapy. The QTc interval should also be monitored because bicarbonate therapy may prolong the QTc. Case reports and an animal model suggest that the use of extracorporeal life support may be lifesaving in TCA overdoses that are refractory to advanced life-support measures and traditional therapies.
• All patients should be monitored for arrhythmias for at least 12 hours, and symptomatic patients should be admitted to an ICU setting.

The local poison control center or a clinical toxicologist should be consulted in all cases of suspected poisoning.

A pediatric psychiatrist should be consulted if intentional ingestion is suspected.

Child protective services should be notified if inadequate supervision or Münchhausen syndrome by proxy is suspected.