What is the management for Amitriptyline (tricyclic antidepressant) toxicity?

Management of Amitriptyline Toxicity

Immediate administration of sodium bicarbonate is the cornerstone of treatment for amitriptyline toxicity with QRS prolongation, ventricular arrhythmias, or hypotension. 1, 2

Initial Assessment and Stabilization

Airway and Breathing

• Secure airway early - intubation is recommended for severe toxicity 1
• Avoid respiratory acidosis in intubated patients as it worsens toxicity 1
• Maintain arterial pH between 7.45-7.55 1

Circulation

• Monitor ECG for:
  • QRS prolongation (>100 ms) - a sensitive indicator of toxicity
  • Terminal 40 ms right axis deviation in lead aVR
  • ST-T wave changes
  • Ventricular arrhythmias

Decontamination

• Perform gastric lavage followed by activated charcoal if presentation is within 1-2 hours of ingestion 3
• EMESIS IS CONTRAINDICATED 3

Treatment Algorithm

First-Line Treatment

1. Sodium Bicarbonate Therapy:

   • Administer 1-2 mEq/kg IV bolus for QRS >100 ms, ventricular arrhythmias, or hypotension 1
   • Repeat doses to maintain arterial pH 7.45-7.55 1
   • Avoid extreme hypernatremia (serum sodium not to exceed 150-155 mEq/L) 2, 1
   • Monitor and treat hypokalemia during alkalemia therapy 1

2. Fluid Resuscitation:

   • Administer 5-10 mL/kg boluses of normal saline for hypotension 1

Second-Line Treatment for Persistent Symptoms

1. For Persistent Hypotension:

   • Epinephrine or norepinephrine (preferred over dopamine) 1
   • Dobutamine may be considered 1

2. For Persistent Ventricular Arrhythmias:

   • Lidocaine 2, 1
   • AVOID Class IA, IC, or III antiarrhythmics (e.g., quinidine, disopyramide, procainamide) as they may worsen toxicity 1, 3

3. For Seizures:

   • Benzodiazepines are first-line treatment 1
   • If ineffective, consider other anticonvulsants 3

Refractory Cases

1. For Refractory Cardiac Toxicity:

   • Consider intravenous lipid emulsion (ILE) therapy 2, 1
   • Magnesium sulfate may be effective for ventricular arrhythmias unresponsive to other treatments 4

2. For Cardiac Arrest or Refractory Shock:

   • Consider extracorporeal membrane oxygenation (VA-ECMO) 2, 1
   • Extended cardiopulmonary resuscitation may be beneficial - cases have reported successful resuscitation after prolonged efforts (up to 70 minutes) 5, 4

Monitoring and Disposition

• Continuous cardiac monitoring for at least 6 hours after ingestion 1
• Close monitoring of electrolytes, particularly potassium 1
• Extended monitoring if signs of toxicity occur at any time 3

Pitfalls and Caveats

• Toxicity can develop rapidly after overdose - hospital monitoring is required as soon as possible 3
• Multiple drug ingestion (including alcohol) is common in deliberate overdose 3
• Patients may succumb to fatal dysrhythmias late after overdose, even with initial improvement 3
• Plasma drug level monitoring should not guide management 3
• Hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis are generally ineffective 3

Special Considerations

• Naloxone has been reported in case studies to be beneficial in severe amitriptyline toxicity, possibly due to effects on opioid receptors 6
• Complications typically develop within 4 hours of admission - this is the most critical monitoring period 7