Why is magnesium given in Tricyclic Antidepressant (TCA) overdose?

Magnesium in TCA Overdose Management

Magnesium sulfate may be considered as an adjunctive treatment in TCA overdose, particularly for patients with ventricular arrhythmias that are refractory to standard treatments, though it is not a first-line therapy according to current guidelines. 1

Pathophysiology of TCA Toxicity

TCA overdose causes toxicity primarily through:

• Blockade of cardiac sodium channels, leading to QRS prolongation, conduction delays, and ventricular arrhythmias 1
• Anticholinergic effects causing sinus tachycardia 2
• Inhibition of neuronal catecholamine uptake 2
• Alpha-adrenergic blockade contributing to hypotension 2

Standard Treatment Protocol for TCA Overdose

The current treatment algorithm for TCA overdose prioritizes:

1. Sodium bicarbonate administration (Class 2a recommendation, Level C-LD evidence)

   • First-line therapy for cardiac arrest or QRS prolongation >120 ms 1
   • Recommended dose: 1-2 mEq/kg (1-2 mL/kg of 8.4% solution) 1
   • Mechanism: Increases extracellular sodium concentration and serum pH, which improves cardiac conduction 1, 2

2. ECMO consideration (Class 2b recommendation, Level C-LD evidence)

   • For cardiac arrest or refractory shock due to TCA toxicity 1
   • Particularly valuable as TCA toxicity is a reversible cause of cardiogenic shock 1

Role of Magnesium in TCA Overdose

Magnesium is not mentioned in first-line recommendations for TCA overdose in current AHA guidelines but may be beneficial for several reasons:

• Antiarrhythmic properties:

  • Increases ventricular fibrillation threshold 3
  • Prolongs sinus node refractoriness and AV node conduction 3
  • May help normalize cardiac rhythm in TCA-induced ventricular arrhythmias 3, 4

• Clinical evidence:

  • One randomized clinical trial showed significantly reduced ICU stay (25.63 ± 9.33 vs 82.67 ± 21.66 hours) when magnesium sulfate was added to standard treatment 5
  • Mortality was lower in the magnesium group (13.9% vs 33.3%), though this approached but did not reach statistical significance (p=0.052) 5
  • Case reports describe successful treatment of refractory ventricular tachycardia with magnesium sulfate when other treatments failed 4

• AHA guidelines note: A clinical trial of magnesium for TCA-induced hypotension, acidosis, and/or QRS prolongation showed better overall outcomes in the magnesium group, but had methodological flaws and no statistically significant effect on mortality 1

When to Consider Magnesium

Magnesium should be considered in TCA overdose in the following scenarios:

• Ventricular arrhythmias refractory to sodium bicarbonate and standard treatments 3, 4
• As an adjunct to sodium bicarbonate in severe cases with persistent QRS prolongation 5
• For polymorphic ventricular tachycardia or torsades de pointes resulting from TCA toxicity 3, 6

Important Caveats

• Magnesium is not a replacement for sodium bicarbonate, which remains the first-line therapy 1
• Stronger evidence supports sodium bicarbonate administration for TCA-induced cardiac toxicity 1
• Magnesium may be most beneficial as part of a comprehensive approach to severe TCA toxicity 5, 3
• Current evidence for magnesium in TCA overdose is limited, with methodological concerns in available studies 1

Practical Considerations

• Magnesium sulfate dosing in TCA overdose is typically similar to that used for other arrhythmias (1-2g IV) 5, 4
• Monitor for side effects of magnesium administration, including hypotension and respiratory depression at high doses 6
• Continue cardiac monitoring throughout treatment as TCA toxicity can persist for days due to the long half-life of these medications 2