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Q1: Recognition and mechanism (3 min)
Examiner: A 26-year-old man presents 90 minutes after taking 2 g of amitriptyline. He is drowsy, pulse 132, BP 88/54, flushed and dry with dilated pupils and absent bowel sounds. ECG: QRS 148 ms, aVR R wave 5 mm, right-axis deviation of the terminal 40 ms. Walk me through the diagnosis and the mechanism. [1][4][7]
Expected answer:
- Diagnosis: severe amitriptyline overdose with cardiotoxicity. Anticholinergic picture plus QRS longer than 100 ms plus RaVR of 3 mm or more.
- Mechanism (at the level of this topic's sources):
- Fast sodium-channel blockade — slowed conduction, QRS widening, ventricular dysrhythmias, hypotension, heart block, seizures and coma. Cardiotoxic effects cause mortality; alkalinisation (preferably sodium bicarbonate) is the treatment of choice once cardiotoxicity is evident. TCAs respond well to bicarbonate, unlike some other sodium-channel blockers (for example bupropion).
- Anticholinergic effects — neurological, cardiac, respiratory and anticholinergic feature categories (Dziukas).
- Boehnert and Lovejoy (NEJM 1985, 49 patients): QRS under 0.10 s — no seizures or ventricular arrhythmias; QRS 0.10 s or longer — 34% seizures and 14% ventricular arrhythmias; ventricular arrhythmias only at 0.16 s or longer. Serum drug levels failed to predict those risks.
- Receptor-level essays (Nav1.5 inner pore, M1, alpha-1, GABA-A) are not in these abstracts — do not recite them as sourced facts. [1][4][7]
Follow-up: Why does the acidosis (pH 7.28) matter? Chan: bicarbonate plus hyperventilation (PCO2 about 30-35 mmHg) achieves serum alkalinisation (pH about 7.45-7.55) at a lower bicarbonate dose and reduces sodium-channel blockade. Acidosis is the state the antidote is reversing. [1][4][7]
Q2: The antidote — sodium bicarbonate (3 min)
Examiner: Give me the indications, dose, end-points, and why bicarbonate works. [1][4][7]
Expected answer:
- ECG indications (Glauser / Woolf): QRS duration more than 100 ms, or terminal right-axis deviation more than 120 degrees; a wide-complex arrhythmia with QRS longer than 100 ms → immediate stabilisation and sodium bicarbonate if a protocol exists.
- Clinical indications (Chan): seizures, shock (SBP under 90 mmHg or MAP under 65 mmHg), or ventricular dysrhythmia.
- Dose: bolus 1-2 mmol/kg (1-2 mEq/kg), repeated if unstable, maximum 6 mmol/kg.
- End-point: serum alkalinisation pH about 7.45-7.55 with hyperventilation (PCO2 about 30-35 mmHg). Stop at the pH target — do not chase complete QRS correction. Excessive dosing until QRS is under 100 ms is a Chan pitfall; even when the QRS responds it takes a few hours to normalise.
- Mechanism in Chan's words: alkalinisation plus sodium loading reduce sodium-channel blockade; synergy with hyperventilation lowers the bicarbonate dose needed.
- A bicarbonate infusion recipe (for example 150 mmol in 850 mL dextrose) is not in these abstracts — do not invent one. [1][4][7]
Follow-up: Pitfalls? Hypernatraemia, fluid overload, metabolic alkalosis and cerebral oedema if exceeding 6 mmol/kg; hypokalaemia and hypocalcaemia (QT prolongation, torsade with mixed-channel drugs); failing to monitor potassium, sodium, pH and the ECG with repeated boluses. [1][4][7]
Q3: Seizures, arrhythmia and the AVOID list (3 min)
Examiner: The patient has a generalised seizure. What do you give, what do you AVOID, and why? [1][4][7]
Expected answer:
- First-line: a benzodiazepine — Woolf Grade D for TCA-associated convulsions. Exact milligram regimens are formulary convention, not in the Woolf abstract.
- Phenytoin is of no benefit in TCA poisoning (Dziukas) — do not upgrade that to an unsourced "worsens sodium-channel blockade".
- A seizure is Chan-significant toxicity and itself an indication for hypertonic bicarbonate within the 6 mmol/kg cap. [1][4][7]
Follow-up — sourced treatments to AVOID:
- Class Ia and class Ic antiarrhythmics — contraindicated. Class II potentially lethal. Class III and IV unproven. Lignocaine is the agent that has been used for ventricular arrhythmias.
- Phenytoin — of no benefit; use a benzodiazepine.
- Flumazenil — not recommended (Woolf). Do not add an unsourced seizure-threshold story.
- Induced emesis — do not (Woolf).
- Physostigmine — no role (Dziukas). Haemodialysis/haemoperfusion — no benefit. [1][4][7]
Q4: Refractory toxicity and escalation (2 min)
Examiner: QRS still wide, BP 78/45 after bicarbonate, refractory ventricular arrhythmia. What next? [1][4][7]
Expected answer — sourced ladder:
- Stay inside Chan's bicarbonate discipline — boluses to the pH target and 6 mmol/kg maximum, with ventilation; do not keep dosing to force QRS under 100 ms.
- Hypertonic saline — Glauser: a promising alternative for severe TCA toxicity.
- Norepinephrine — Teba: rescued two hypotensive TCA overdoses unresponsive to fluid challenge and dopamine over 15 micrograms/kg/min.
- Intravenous lipid emulsion — rescue when deterioration continues despite standard therapy including sodium bicarbonate (Hendron; Levine). Anticipate pancreatitis and hours of uninterpretable laboratories (Levine). Do not recite an unsourced 1.5 mL/kg / 0.25 mL/kg/min protocol.
- Lignocaine for ventricular arrhythmias; avoid Ia/Ic.
- Do not reach for dialysis. [1][4][7]
Q5: Disposition, special populations and pitfalls (2 min)
Examiner: How do you decide on disposition, and what is different in children? [1][4][7]
Expected answer:
- Six-hour rule (Dziukas, not GEMNet from these abstracts): life-threatening complications develop within six hours of overdose or not at all.
- Woolf unintentional ingestions: asymptomatic patients are unlikely to develop symptoms if more than 6 hours have passed — they do not need emergency-department referral. Any symptom after TCA ingestion warrants referral. Self-harm → ED immediately.
- QRS longer than 100 ms on an ECG or rhythm strip → immediate stabilisation and bicarbonate.
- Paediatrics: children under 6 need evaluation after any TCA ingestion (Woolf). Hendron: a 20-month-old with potentially lethal dothiepin deteriorated despite standard paediatric TCA therapy and survived after lipid emulsion plus bicarbonate plus cardioversion.
- Delayed toxicity exists in severe cases (Levine: delayed seizures and arrest after amitriptyline in a 13-year-old) — symptomatic or ECG-abnormal patients are never discharged on the clock alone.
- Psychiatric assessment after medical clearance for deliberate overdose. Woolf/Hawton: toxicity differences matter for prescribing in people at risk. [1][4][7]
References12ShowHide
- [1]Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, Wax PM, Manoguerra AS, Scharman EJ, Olson KR, Chyka PA, Christianson G, Troutman WG. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management Clin Toxicol (Phila), 2007.PMID 17453872
- [2]Boehnert MT, Lovejoy FH Jr. Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants N Engl J Med, 1985.PMID 4022081
- [3]Liebelt EL, Francis PD, Woolf AD. ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity Ann Emerg Med, 1995.PMID 7618783
- [4]Dziukas LJ, Vohra J. Tricyclic antidepressant poisoning Med J Aust, 1991.PMID 2017063
- [5]Glauser J. Tricyclic antidepressant poisoning Cleve Clin J Med, 2000.PMID 11060957
- [6]Groleau G, Jotte R, Barish R. The electrocardiographic manifestations of cyclic antidepressant therapy and overdose: a review J Emerg Med, 1990.PMID 2254609
- [7]Chan BS, Buckley NA. Common pitfalls in the use of hypertonic sodium bicarbonate for cardiac toxic drug poisonings Clin Toxicol (Phila), 2024.PMID 38597366
- [8]Hawton K, Bergen H, Simkin S, Cooper J, Waters K, Gunnell D, Kapur N. Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose Br J Psychiatry, 2010.PMID 20435959
- [9]Taylor D, Poulou S, Clark I. The cardiovascular safety of tricyclic antidepressants in overdose and in clinical use Ther Adv Psychopharmacol, 2024.PMID 38827015
- [10]Hendron D, Menagh G, Sandilands EA, Scullion D. Tricyclic antidepressant overdose in a toddler treated with intravenous lipid emulsion Pediatrics, 2011.PMID 22065274
- [11]Levine M, Brooks DE, Franken A, Graham R. Delayed-onset seizure and cardiac arrest after amitriptyline overdose, treated with intravenous lipid emulsion therapy Pediatrics, 2012.PMID 22753554
- [12]Teba L, Schiebel F, Dedhia HV, Lazzell VA. Beneficial effect of norepinephrine in the treatment of circulatory shock caused by tricyclic antidepressant overdose Am J Emerg Med, 1988.PMID 3178947