Tricyclic Antidepressant Overdose with Sodium Channel Blockade
A 22-year-old woman is brought in 90 minutes after ingesting an unknown quantity of her mother's amitriptyline in a suicide attempt. She is drowsy but responds to painful stimulation, with a Glasgow Coma Scale score of 12. Vital signs: blood pressure 82/46 mmHg, heart rate 128/min, respiratory rate 22/min, temperature 37.4 °C, SpO₂ 96% on room air. ECG shows sinus tachycardia, QRS duration 148 ms, a terminal R wave in aVR and a prolonged QT interval. She has had one brief generalised seizure in the emergency department. Bedside glucose is 110 mg/dL; arterial blood gas pH 7.31, PaCO₂ 34 mmHg, bicarbonate 17 mmol/L; lactate 4.1 mmol/L, potassium 4.6 mmol/L, creatinine 1.1 mg/dL. She has not vomited, and activated charcoal was not given. She is becoming more somnolent, and the team is considering intubation.
1. Outline your immediate treatment priorities, including the dose, target and mechanism of sodium bicarbonate therapy.
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Priority. This is a tricyclic overdose with the dangerous triad of sodium channel blockade (QRS 148 ms), hypotension and seizure. Cardiovascular collapse, not the ingested dose, determines urgency.
Sodium bicarbonate. Give 1–2 mmol/kg of 8.4% sodium bicarbonate as an intravenous bolus (in a 60 kg patient, roughly 60–120 mmol, i.e. 1–2 ampoules). Repeat boluses until the QRS narrows below 120 ms or the blood pressure improves, then begin an infusion of three ampoules (150 mmol) in 1 L of 5% dextrose at 1.5–2 mL/kg/h. Monitor arterial pH every 30–60 minutes and aim for pH 7.45–7.55.
Why it works. There are two mechanisms. Sodium loading overcomes competitive block of the fast sodium channel, and alkalinisation increases the fraction of drug bound to plasma proteins while reducing the free drug available to the myocardium. Both effects narrow the QRS and stabilise the membrane.
Other immediate measures. Treat the seizure with a benzodiazepine (for example lorazepam or diazepam), since seizures worsen acidosis, which in turn worsens cardiotoxicity. Support blood pressure with a norepinephrine infusion, using small fluid boluses cautiously. Correct hypoxia and hypercarbia aggressively, because both worsen sodium channel blockade. Do not give flumazenil or physostigmine. Obtain serial ECGs and consider activated charcoal only if the airway is protected and the ingestion is within about 1–2 hours - here the window is already closing and the airway is not secure.
2. How would you approach the airway? Which induction agents and drugs would you choose or avoid, and how would you ventilate her after intubation?
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Indication. She has a falling conscious level, a seizure, and a need for controlled ventilation to manage acidosis. A GCS of 12 with progressive somnolence and an unreliable airway after a seizure and possible aspiration is sufficient reason to intubate before she deteriorates further, not after.
Preparation. Preoxygenate carefully and correct hypoxia first; hypoxaemia and hypercarbia both potentiate tricyclic cardiotoxicity. Have push-dose or infusion norepinephrine ready, and assume post-intubation hypotension.
Induction. Ketamine 1–2 mg/kg or etomidate 0.3 mg/kg maintains haemodynamic stability and is preferred. Avoid propofol, which causes vasodilation and hypotension in a patient already vasoplegic from sodium channel blockade. Rocuronium is a reasonable neuromuscular blocker; succinylcholine is not contraindicated by tricyclic overdose itself but should be avoided if there is hyperkalaemia or a long immobile period.
Ventilation. After intubation, use controlled ventilation to keep pH 7.45–7.55 with a PaCO₂ around 30–35 mmHg; hyperventilation is a therapeutic manoeuvre, not just a side effect. Avoid high airway pressures. Continue the bicarbonate infusion, recheck arterial gases and electrolytes frequently (watch for hypernatraemia and hypokalaemia), and treat hypotension with norepinephrine before large fluid volumes. Never give flumazenil in a mixed overdose, and avoid class IA and IC antiarrhythmics.
3. Despite bicarbonate and norepinephrine, she remains hypotensive with recurrent wide-complex rhythm. What rescue therapies would you consider, what would you avoid, and how long would you monitor her?
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Rescue therapy. Consider intravenous lipid emulsion 20% at 1.5 mL/kg as a bolus, followed by an infusion of 0.25 mL/kg/min for 30–60 minutes, for refractory cardiovascular collapse. It is not first-line and the evidence is largely from case series, but it is reasonable when standard therapy is failing; watch for interference with laboratory assays and for pancreatitis. Correct electrolytes, continue bicarbonate boluses for any QRS widening, and consider magnesium only if there is torsades, not for routine wide-complex tachycardia. If she remains in refractory shock, discuss extracorporeal support with a toxicology and critical care team early.
What to avoid. Do not give class IA antiarrhythmics (procainamide, quinidine, disopyramide) or class IC agents (flecainide, propafenone), because they add to sodium channel blockade. Avoid flumazenil and physostigmine, which can precipitate seizures and arrhythmias. Avoid large fluid boluses in a patient with impaired myocardial contractility, and avoid unopposed beta-blockade.
Monitoring. Admit to a monitored bed or ICU. A patient with a wide QRS, seizure or arrhythmia needs at least 24 hours of continuous cardiac monitoring and serial ECGs, because delayed arrhythmias occur after initial improvement. A patient with no symptoms, a normal QRS and normal ECG at 6 hours may be medically cleared after psychiatric assessment. Arrange toxicology follow-up, a psychiatric assessment before discharge, and safeguarding for the source of the tablets.