How does sodium bicarbonate help in Tricyclic Antidepressant (TCA) poisoning?

Sodium Bicarbonate in TCA Poisoning

Sodium bicarbonate is the first-line antidote for life-threatening TCA poisoning, working through dual mechanisms of sodium loading and alkalinization to reverse cardiac sodium channel blockade, reduce QRS prolongation, and treat hypotension and ventricular dysrhythmias. 1

Mechanisms of Action

Sodium bicarbonate achieves therapeutic benefit through two synergistic mechanisms:

• Sodium loading: Increases extracellular sodium concentration, which overcomes the sodium channel blockade caused by TCAs and improves cardiac conduction 1
• Alkalinization: Raising serum pH reduces the active (ionized) fraction of TCAs, decreasing their binding to cardiac sodium channels and reversing cardiotoxicity 2, 3

The combination of both mechanisms produces an additive effect superior to either intervention alone 1, 2

Clinical Indications

Administer sodium bicarbonate for TCA poisoning when any of the following are present:

• QRS duration >100-120 milliseconds on ECG 4, 5
• Hypotension (systolic BP <90 mmHg or MAP <65 mmHg) despite adequate fluid resuscitation 3
• Ventricular dysrhythmias 1, 3
• Seizures associated with TCA toxicity 3
• Terminal rightward axis deviation >120 degrees in lead aVR 1, 5

Dosing Protocol

Initial Bolus Dosing

• Adults: 1-2 mEq/kg (1-2 mL/kg of 8.4% solution) IV, administered as hypertonic solution (1000 mEq/L) 1, 6
• Children: 1-2 mEq/kg IV given slowly 6
• Repeat boluses as needed until clinical stability is achieved 1, 5

Maintenance Therapy

• After initial bolus, continue with infusion of 150 mEq/L solution at 1-3 mL/kg/hour to maintain alkalosis 6
• Titrate to resolution of hypotension and QRS prolongation 1

Maximum Dosing Limits

• Do not exceed 6 mmol/kg total dose to avoid hypernatremia, fluid overload, metabolic alkalosis, and cerebral edema 3

Target Parameters and Monitoring

Achieve and maintain the following therapeutic targets:

• Serum pH: 7.45-7.55 (avoid exceeding 7.50-7.55) 1, 3
• Serum sodium: <150-155 mEq/L (avoid hypernatremia) 1
• PCO2: 30-35 mmHg through mechanical hyperventilation if intubated 3

Critical Monitoring Parameters

• Serial arterial blood gases for pH and PCO2 3
• Serum electrolytes, particularly potassium and calcium (sodium bicarbonate causes hypokalemia and hypocalcemia) 1, 3
• Continuous ECG monitoring for QRS duration and dysrhythmias 4

Synergistic Strategy with Hyperventilation

For intubated patients, combine sodium bicarbonate with mechanical hyperventilation to achieve optimal alkalinization while minimizing bicarbonate dose and adverse effects 3:

• Target PCO2 of 30-35 mmHg through increased minute ventilation 3
• This synergistic approach reduces the total sodium bicarbonate dose required 3
• Alkalinization is best achieved through combined respiratory and metabolic alkalosis 3

Common Pitfalls and Caveats

Avoid Excessive Dosing

• Do not continue dosing until QRS <100 ms - this leads to overdosing, as QRS normalization takes hours even after adequate alkalinization 3
• QRS prolongation is not specific for sodium channel blockade and may represent rate-dependent bundle branch block 3
• Stop further doses once target pH of 7.45-7.55 is achieved 3

Electrolyte Complications

• Monitor and aggressively correct hypokalemia during alkalemia therapy, as this is common and can worsen cardiotoxicity 1, 3
• Hypocalcemia can occur and may prolong QT interval, potentially causing torsade de pointes in mixed sodium/potassium channel blocker poisonings 3

Drug Incompatibilities

• Never mix sodium bicarbonate with catecholamines (epinephrine, norepinephrine) or calcium-containing solutions, as it inactivates these medications 6
• Administer through separate IV lines 6

Fluid Management

• Begin with crystalloid or colloid resuscitation guided by central venous pressure before administering sodium bicarbonate 2
• Sodium bicarbonate can cause significant sodium and fluid overload 6

Adjunctive Therapies

If hypotension persists despite adequate filling pressures and sodium bicarbonate:

• Epinephrine is superior to norepinephrine for TCA-induced shock, with higher survival rates when combined with sodium bicarbonate 2
• Norepinephrine and dopamine have shown clinical benefit 2
• Consider VA-ECMO for refractory cardiogenic shock (Class 2a recommendation) 1

For refractory ventricular dysrhythmias after sodium bicarbonate:

• Lidocaine (Class Ib antidysrhythmic) may be used as second-line therapy 1
• Avoid Class Ia and Ic antidysrhythmics (worsen sodium channel blockade) and beta-blockers (precipitate hypotension and arrest) 2

For seizures associated with TCA poisoning:

• Benzodiazepines (diazepam or midazolam) are first-line 4