Tricyclic Antidepressant Overdose — SAQ

Stem

A 26-year-old man is brought to the emergency department by ambulance 90 minutes after a deliberate overdose of amitriptyline. He took forty tablets of amitriptyline 50 mg (2 g) from a recently filled prescription, with an unknown quantity of alcohol. On arrival he is drowsy but rousable. ^[1][4][7]

On examination: pulse 132/min, blood pressure 88/54 mmHg, respiratory rate 14/min, oxygen saturation 94 percent on air, GCS 12, temperature 38.1 C. Skin is flushed, hot and dry; pupils are dilated and sluggish; mucosae are dry; bowel sounds are absent; the bladder is palpable. ^[1][4][7]

12-lead ECG: sinus tachycardia, QRS 148 ms, PR 220 ms, QT 480 ms, with a terminal R wave of 5 mm in aVR and right-axis deviation of the terminal 40 ms. Venous gas: pH 7.28, lactate 4.1 mmol/L. ^[1][4][7]

Questions

a) What is the diagnosis, and state FOUR features in the stem that support it. (2 marks) ^[1][4][7]

Diagnosis: severe tricyclic-antidepressant (amitriptyline) overdose with cardiotoxicity. Supporting features (any four):

1. The anticholinergic picture — mydriasis, dry/hot/flushed skin, absent bowel sounds, palpable bladder, fever (major feature category of overdose).
2. QRS widening to 148 ms — longer than 100 ms, the ECG screen that predicts seizures/arrhythmias and prompts sodium bicarbonate.
3. Terminal R wave of 5 mm in aVR (3 mm or more) — the only independent ECG predictor of seizures and arrhythmias in the Liebelt cohort.
4. Hypotension (88/54) — a classical cardiovascular manifestation and a Chan indication for hypertonic bicarbonate (shock: SBP under 90 mmHg).
5. Known amitriptyline ingestion well above the Woolf out-of-hospital referral threshold (over 5 mg/kg for most TCAs). ^[1][4][7]

b) Describe how amitriptyline produces cardiotoxicity and the anticholinergic picture. (3 marks) ^[1][4][7]

1. Fast sodium-channel blockade (the cardiotoxic mechanism). Cyclic antidepressants slow intraventricular conduction. The ECG consequence is QRS widening, with ventricular dysrhythmias, hypotension, heart block, seizures and coma as the classical manifestations; it is predominantly the cardiotoxic effects that cause mortality. Once cardiotoxicity is evident, serum alkalinisation, preferably by sodium bicarbonate, is the treatment of choice. Tricyclic poisoning is a sodium-channel-blocker poisoning that responds well to sodium bicarbonate.
2. Anticholinergic (antimuscarinic) effects. The major features of overdose are neurological, cardiac, respiratory and anticholinergic — dry-hot-flushed-delirious picture, mydriasis, ileus and urinary retention.
3. Why the acidosis matters (paired with the antidote). Chan: hypertonic bicarbonate works synergistically with hyperventilation (PCO2 about 30-35 mmHg) to reach serum pH about 7.45-7.55 and reduce sodium-channel blockade. Receptor-level names (Nav1.5 pore, M1, alpha-1, GABA-A) are conventional teaching and are not in this topic's sourced abstracts — do not invent them as exam numbers. ^[1][4][7]

c) Outline the immediate stepwise management, with sourced doses and end-points. (4 marks) ^[1][4][7]

1. ABCDE — coma, convulsions, respiratory depression and hypotension with standard resuscitation techniques and drugs; fluids, cardiovascular agents and respiratory support per ACLS. Ventilate with the antidote in mind: hyperventilation to PCO2 about 30-35 mmHg.
2. IV sodium bicarbonate — the antidote. This patient meets Glauser/Woolf ECG criteria (QRS over 100 ms; terminal RAD over 120 degrees) and Chan clinical criteria (shock). Bolus 1-2 mmol/kg (1-2 mEq/kg), repeated if unstable, maximum 6 mmol/kg. End-point is serum alkalinisation (pH about 7.45-7.55), NOT complete QRS correction — chasing QRS under 100 ms is a documented pitfall. Monitor and correct potassium and sodium.
3. Decontamination — activated charcoal 30-50 g once the airway is protected (Glauser); Dziukas recommended charcoal for all. Do NOT induce emesis (Woolf).
4. Seizures — benzodiazepines are recommended; phenytoin is of no benefit (do not claim a sodium-channel mechanism that is not in the cited abstracts).
5. Vasopressors — hypotension unresponsive to fluid and dopamine may respond to norepinephrine (Teba: two cases after dopamine over 15 micrograms/kg/min failed).
6. Escalation — intravenous lipid emulsion when the patient continues to deteriorate despite standard therapy including sodium bicarbonate (Hendron toddler dothiepin; Levine delayed amitriptyline arrest). Sourced papers do not specify a 1.5 mL/kg recipe — do not invent one. Haemodialysis/haemoperfusion are of no benefit.
7. Monitored admission. Life-threatening complications develop within six hours of overdose or not at all. ^[1][4][7]

d) State THREE treatments you must AVOID in this patient, with the sourced reason for each. (1 mark) ^[1][4][7]

1. Class Ia (procainamide, quinidine, disopyramide) and class Ic (flecainide) — contraindicated; class II potentially lethal; class III/IV unproven (Dziukas). Lignocaine is the antiarrhythmic that has been used. ^[4]
2. Phenytoin for seizures — of no benefit in TCA poisoning; use a benzodiazepine. ^[4]
3. Flumazenil — not recommended in TCA poisoning. Also: do not induce emesis; physostigmine has no role; dialysis is of no benefit. ^[1][4][7]

Model answer marking points

^{[1] [4] [5] [7]}

References12ShowHide

1. [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. [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. [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. [4]Dziukas LJ, Vohra J. Tricyclic antidepressant poisoning Med J Aust, 1991.PMID 2017063
5. [5]Glauser J. Tricyclic antidepressant poisoning Cleve Clin J Med, 2000.PMID 11060957
6. [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. [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. [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. [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. [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. [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. [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