Review Question - QID 105639

This patient with hyperthermia, tachycardia, flushing and mydriasis with an electrocardiogram demonstrating a widened QRS complex has likely taken an overdose of a tricyclic antidepressant medication. For patients with suspected tricyclic antidepressant (TCA) overdose and widening of the QRS complex, the most appropriate next step in management is administration of sodium bicarbonate.

TCAs have anticholinergic. anti-alpha-adrenergic, anti-histamine, and sodium channel blocking properties, which contribute to their side effects and toxicity. The classic toxicity profile for TCAs can be remembered with the 3 C's: convulsions, coma, and cardiotoxicity. Cardiotoxicity is the best predictor for TCA overdose and manifests as QRS prolongation. When ECG changes are noted, the patient should be treated with IV sodium bicarbonate, which acts to alkalinize the plasma and promote dissociation of the neutral form of the drug from sodium channels.

Adams et al. describe the approach to treatment of depression and explain that, as there is no marked difference between the effectiveness of each medication, medications should be prescribed on an individual basis by tailoring the benefits and side effects of each medication to best suit the patient. They state that TCAs are metabolized in the liver by the cytochrome P450 enzymes, and genetic variations in the activity of P450 can lead to variable blood levels of TCAs for different patients.

Pierog et al. present a case report of a patient with TCA toxicity who was treated with sodium bicarbonate therapy. They describe the importance of directing sodium bicarbonate therapy based on ECG and vital signs. They challenge the recommended dose of sodium bicarbonate, stating that the dose is too small and that the dosing should rather be mediated by the patient's clinical presentation.

Figure A shows an electrocardiogram with features consistent with TCA overdose. The two most pertinent findings are QRS prolongation and tachycardia.
Illustration A demonstrates the mechanism of action of TCAs. TCAs work primarily by blocking the reuptake of norepinepherine and serotonin. Illustration B lists the main side effects of TCAs

Incorrect answers:
Answer 1: Magnesium is given for patients with Torsades de Pointes, a form of polymorphic ventricular tachycardia that results from terminal QT interval prolongation. This patient's electrocardiogram does not demostrate Torsades de Pointes, and magnesium is not indicated in the management of suspected TCA overdose.

Answer 2: N-acetylcysteine is given for acetaminophen overdose to restore reduced gluathione stores. Acetaminophen overdose often presents without symptoms or with abdominal pain. Acetmainophen overdose does not cause widening of the QRS complex.

Answer 3: Naloxone is indicated for management of suspected opiate overdose. Miosis and bradypnea or apnea would be expected. Electrocardiogram changes such as QRS complex widening would not be expected.

Answer 4: Physostigmine is indicated in the management of some patients with anticholinergic toxicity. However, despite the anticholinergic effects of TCAs, physostigmine is associated with an increased risk of cardiac arrest and is therefore contraindicated.

Bullet Summary:
For patients with suspected tricyclic antidepressant (TCA) overdose and widening of the QRS complex, the most appropriate next step in management is administration of sodium bicarbonate.