What is the role of bicarbonate (sodium bicarbonate) in managing tricyclic antidepressant overdose?

Role of Sodium Bicarbonate in Managing Tricyclic Antidepressant Overdose

Sodium bicarbonate is the mainstay of therapy for tricyclic antidepressant overdose with cardiac conduction abnormalities and should be administered promptly to treat life-threatening cardiotoxicity. 1

Mechanism of Cardiotoxicity in TCA Overdose

• Tricyclic antidepressants block cardiac sodium channels, causing QRS prolongation, hypotension, seizures, ventricular dysrhythmias, and cardiovascular collapse 1
• Characteristic ECG changes include intraventricular conduction delay (QRS interval prolongation) and terminal rightward axis deviation in lead aVR, which typically precede ventricular dysrhythmias 1
• TCA overdose is the most common cause of death from prescription drugs, with highly toxic levels manifested as QRS prolongation ≥100 milliseconds 2

Treatment Recommendations

First-Line Treatment

• Administer hypertonic sodium bicarbonate (Class 1, Level B-NR recommendation) for life-threatening cardiotoxicity from tricyclic antidepressant poisoning 1
• Typical dosing: 1-2 mmol/kg IV bolus of hypertonic sodium bicarbonate (8.4%, 1 mEq/mL), which can be repeated if the patient remains unstable 1, 3
• Titrate sodium bicarbonate boluses to resolution of hypotension and QRS prolongation 1
• Maximum recommended dose is 6 mmol/kg to avoid complications such as hypernatremia, fluid overload, and metabolic alkalosis 3

Mechanism of Action

• Sodium bicarbonate works through two mechanisms: sodium loading and increasing serum pH (alkalinization) 1, 4
• Both mechanisms have an additive effect in reducing cardiotoxicity 1
• Some experimental studies suggest sodium loading is the primary mechanism, while others indicate pH change is more important 4, 5

Monitoring and Targets

• Target serum pH of 7.45-7.55 3, 4
• Avoid extreme hypernatremia (serum sodium not to exceed 150-155 mEq/L) 1
• Monitor and correct electrolyte abnormalities, particularly hypokalemia and hypocalcemia, which can occur during alkalinization therapy 1, 3
• When mechanical ventilation is required, avoid respiratory acidosis 1
• Consider hyperventilation (PCO₂ ~30-35 mmHg) in conjunction with sodium bicarbonate to achieve optimal alkalinization with lower doses 3

Additional Management Considerations

Vasopressors for Persistent Hypotension

• If hypotension persists despite adequate fluid resuscitation and sodium bicarbonate administration, initiate vasopressor support 4
• Vasopressors associated with improvement in tricyclic-induced hypotension include:
  • Norepinephrine 1
  • Epinephrine 1
  • Dopamine 1
  • Dobutamine 1

Alternative Therapies for Refractory Cases

• For refractory cases, consider:
  • Lidocaine (Class 2b, Level C-LD) may be reasonable to treat life-threatening cardiotoxicity from TCA poisoning 1
  • Extracorporeal life support, such as VA-ECMO (Class 2a, Level C-LD) for refractory cardiogenic shock 1
  • Intravenous lipid emulsion (Class 2b, Level C-LD) for life-threatening sodium channel blocker poisoning refractory to other treatments 1

Cautions and Contraindications

• Avoid class Ia and Ic antiarrhythmics as they may worsen sodium channel blockade 1, 4
• Avoid beta-blockers as they may precipitate hypotension and cardiac arrest 4
• Monitor for hypokalemia during alkalemia therapy, as this can lead to additional cardiac complications 1
• Excessive sodium bicarbonate administration can cause hypernatremia, fluid overload, metabolic alkalosis, and cerebral edema 3

Case Example of Extreme Requirement

• In rare cases, patients may require unusually high doses of sodium bicarbonate. One case report documented successful treatment with 2650 mEq of sodium bicarbonate for refractory QRS widening 6

Common Pitfalls to Avoid

• Continuing to administer sodium bicarbonate until QRS duration is <100 ms may lead to excessive dosing, as QRS normalization can take hours even with effective treatment 3
• Failing to recognize that QRS prolongation may be due to rate-dependent bundle branch block rather than sodium channel blockade 3
• Not monitoring for electrolyte abnormalities, particularly hypokalemia, which can occur during alkalinization therapy 1, 3
• Overlooking the need to avoid respiratory acidosis in mechanically ventilated patients 1