How should I manage an acute amitriptyline overdose in a patient who is obtunded with airway compromise, respiratory depression, hypotension, seizures, and prolonged QRS duration?

Management of Amitriptyline Poisoning

Secure the airway immediately with endotracheal intubation in any obtunded patient with airway compromise, then administer intravenous sodium bicarbonate boluses (1-2 mEq/kg) to achieve and maintain arterial pH >7.45-7.55, while providing aggressive supportive care for seizures, hypotension, and dysrhythmias. 1

Immediate Airway and Breathing Management

Airway control is the absolute first priority and must precede all other interventions. 2

• Intubate immediately if the patient is obtunded with airway compromise or respiratory depression; do not delay for pharmacologic interventions. 2
• Provide bag-mask ventilation with 100% oxygen if intubation is not immediately available, maintaining ventilatory support until the airway is definitively secured. 2, 3
• Position the patient to optimize airway patency (head-tilt/chin-lift or jaw-thrust) while preparing for intubation. 2
• Verify endotracheal tube position, patency, and security immediately after placement, and obtain arterial blood gases 10-15 minutes after establishing mechanical ventilation. 1

Sodium Bicarbonate Therapy for Cardiac Toxicity

Sodium bicarbonate is the cornerstone antidote for tricyclic antidepressant toxicity and must be administered aggressively for QRS prolongation, ventricular dysrhythmias, or hypotension. 1

• Give 1-2 mEq/kg intravenous boluses of sodium bicarbonate until arterial pH reaches >7.45. 1
• Provide a continuous infusion of 150 mEq NaHCO₃ per liter of D5W to maintain alkalosis. 1
• In severe intoxication, increase the target pH to 7.50-7.55 to maximize sodium channel blockade reversal. 1
• The alkalinization works through two mechanisms: increased serum sodium overcomes sodium channel blockade, and alkalemia reduces the active (charged) fraction of the drug. 1

Seizure Management

Treat seizures immediately with benzodiazepines as first-line therapy. 1

• Administer intravenous benzodiazepines (lorazepam 0.1 mg/kg or diazepam 0.2 mg/kg) for any seizure activity. 1
• Continue sodium bicarbonate therapy, as alkalinization may help prevent recurrent seizures. 1
• Do not use Class IA, IC, or III antiarrhythmics (quinidine, procainamide, flecainide, propafenone, amiodarone, sotalol), as these will exacerbate cardiac toxicity. 1

Hypotension Management

Treat hypotension aggressively with fluid resuscitation followed by direct-acting vasopressors if needed. 1

• Give 10 mL/kg boluses of normal saline for initial fluid resuscitation. 1
• If hypotension persists despite adequate fluid resuscitation, epinephrine and norepinephrine are more effective than dopamine for raising blood pressure in tricyclic antidepressant toxicity. 1
• Continue sodium bicarbonate therapy, as alkalinization may improve blood pressure by reversing myocardial depression. 1
• Consider ECMO if high-dose vasopressors fail to maintain adequate blood pressure. 1

Cardiac Monitoring and Dysrhythmia Management

Continuous cardiac monitoring is mandatory, with specific attention to QRS duration and rhythm abnormalities. 1

• Monitor for QRS prolongation, QT interval prolongation, heart block, bradycardia, ventricular tachycardia, torsades de pointes, and ventricular fibrillation. 1
• Sodium bicarbonate is the primary treatment for ventricular dysrhythmias; administer 1-2 mEq/kg boluses in addition to standard ACLS protocols. 1
• Avoid Class IA, IC, and III antiarrhythmics entirely, as they share sodium channel blocking properties and will worsen toxicity. 1
• For refractory ventricular dysrhythmias despite maximal alkalinization, consider lidocaine (Class IIb recommendation), though evidence is limited. 1

Supportive Care and Monitoring

Provide comprehensive supportive care with continuous reassessment. 1

• Maintain standard monitoring including continuous ECG, pulse oximetry, blood pressure, and capnography if intubated. 1
• Obtain serial arterial blood gases to guide sodium bicarbonate therapy and ensure adequate pH targets are maintained. 1
• Monitor serum electrolytes, particularly potassium, as alkalinization can cause hypokalemia. 1
• Keep the patient in a monitored setting (ICU) until QRS duration normalizes and cardiovascular stability is achieved for at least 24 hours. 1

Critical Pitfalls to Avoid

• Never delay intubation in an obtunded patient while attempting other interventions; airway compromise is immediately life-threatening. 2, 3
• Never use antiarrhythmic drugs (Class IA, IC, or III agents) for dysrhythmias, as they will worsen sodium channel blockade. 1
• Never rely on dopamine alone for hypotension; direct-acting vasopressors (epinephrine, norepinephrine) are superior. 1
• Never discharge or downgrade monitoring until the QRS has normalized and the patient has been cardiovascularly stable for at least 24 hours, as late deterioration can occur. 1
• Never withhold sodium bicarbonate in the presence of QRS prolongation >100 ms, ventricular dysrhythmias, or hypotension, even if the pH is already normal. 1

Observation Period

All patients with amitriptyline overdose require prolonged observation in an intensive care setting. 1

• Minimum observation of 24-48 hours after cardiovascular stability is achieved and QRS duration normalizes. 1
• Tricyclic antidepressants have prolonged elimination half-lives and can cause delayed toxicity or recurrence after apparent improvement. 1