ICU · toxicology

Acute Tricyclic Antidepressant (TCA) Poisoning — Comprehensive ICU Management

Also known as Tricyclic antidepressant poisoning · TCA overdose · Amitriptyline overdose · Sodium channel blockade poisoning · Sodium bicarbonate antidote · Membrane stabilising agent toxicity · Wide QRS toxicology · Lipid emulsion rescue

Acute tricyclic antidepressant (TCA) poisoning — the classic 'membrane stabilising' overdose. Five pharmacological actions converge: (1) FAST SODIUM CHANNEL BLOCKADE (use-dependent, phase 0 of His-Purkinje/myocardial depolarisation) → slowed conduction → WIDE QRS, prolonged PR, right-axis deviation with terminal R in aVR/V1 (RBBB pattern) → decreased contractility + re-entrant VENTRICULAR TACHYARRHYTHMIAS (VT/VF) — THIS IS THE LETHAL MECHANISM; (2) POTASSIUM CHANNEL (IKr) BLOCKADE → QT PROLONGATION → torsades de pointes; (3) ALPHA-1 ADRENERGIC BLOCKADE → vasodilation → HYPOTENSION (the haemodynamic driver); (4) ANTICHOLINERGIC (muscarinic) blockade → the toxidrome 'MAD AS A HATTER, BLIND AS A BAT, DRY AS A BONE, RED AS A BEET, HOT AS A HARE — the bowel and bladder lose their tone and the heart runs alone' (delirium, mydriasis, dry mucosae, anhidrosis, urinary retention, ileus, sinus tachycardia, hyperthermia); (5) NORADRENALINE/SEROTONIN REUPTAKE INHIBITION (the therapeutic action) → early transient hypertension, myoclonus, hyperreflexia. GABA-A antagonism → SEIZURES. Agents: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, dothiepin/dosulepin (MOST cardiotoxic), doxepin, trimipramine; lofepramine (LEAST cardiotoxic). Severity = an ECG problem, not a drug level: QRS >100 ms = sodium channel blockade = cardiotoxicity = risk of VT/VF; QRS >160 ms = very high arrhythmia risk; R wave in aVR >3 mm or R/S ratio in aVR >0.7 predicts seizures and arrhythmias. Toxic dose: >5 mg/kg mild, >10 mg/kg significant, >15–20 mg/kg potentially lethal (amitriptyline 5 g in a 70 kg adult ≈ 71 mg/kg = SEVERE). Most toxicity declares within 6 h of ingestion; an asymptomatic patient with a normal ECG at 6 h is very unlikely to deteriorate. Management: SODIUM BICARBONATE 1–2 mmol/kg IV BOLUS — the ANTIDOTE — TARGET QRS <100 ms (titrate to QRS, NOT to pH). Sodium loading overcomes fast Na-channel blockade (mass-action effect, increased extracellular [Na+] restores the depolarisation gradient); alkalosis (target pH 7.45–7.55) increases plasma-protein binding of TCA → reduces free active drug. Repeat bicarbonate boluses as needed + maintenance infusion + hyperventilation. Hypotension: IV fluids then NORADRENALINE (direct alpha agonist overcomes alpha-1 blockade; AVOID adrenaline/salbutamol — beta-2 vasodilation worsens it). Seizures: BENZODIAZEPINES. Ventricular arrhythmia: BICARBONATE FIRST + correct acidosis/hypokalaemia. AVOID class Ia antiarrhythmics (quinidine, procainamide, disopyramide) and amiodarone — they EXTEND Na-channel blockade/widen QRS. AVOID flumazenil — lowers seizure threshold → seizures. AVOID physostigmine — bradycardia/asystole. Activated charcoal 50 g if <1 h and airway protected. Lipid emulsion 20% (1.5 mL/kg bolus then 0.25 mL/kg/min) for REFRACTORY cardiotoxicity. NOT dialysable (large Vd, high protein binding). Mortality now <1% with optimal care; death is usually early arrhythmia/hypotension.

high6 referencesUpdated 2 July 2026

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Red flags

QRS >100 ms after TCA ingestion = SODIUM CHANNEL BLOCKADE = cardiotoxicity — give IV sodium bicarbonate 1–2 mmol/kg and repeat until QRS <100 msHypotension + wide QRS after TCA = life-threatening — bicarbonate + IV fluids + NORADRENALINE (not adrenaline)AVOID class Ia antiarrhythmics (quinidine, procainamide, disopyramide) and amiodarone — they worsen Na-channel blockade and widen QRSAVOID flumazenil — lowers the seizure threshold and TCA already causes seizures via GABA-A antagonismAVOID physostigmine — bradycardia/asystole in TCA cardiotoxicityTCA poisoning is NOT dialysable — large Vd and high protein binding. Treat with bicarbonate, not haemodialysis (contrast with salicylate)Dothiepin/dosulepin and clomipramine are the MOST cardiotoxic TCAs; lofepramine the least

Your progress

Saved locally on this device.

Target exams

CICMFFICMEDIC

Red flags

Overview

Pathophysiology diagram for tca-poisoning-comprehensive-icu — FigureCore mechanisms examiners expect in CICM/FFICM/EDIC answers.

Management algorithm for tca-poisoning-comprehensive-icu — FigureStepwise ICU management: immediate priorities, disease-specific therapy, escalation.

The one-paragraph exam answer

TCA poisoning = a membrane-stabilising (fast sodium-channel blocking) overdose with five converging actions: (1) fast Na-channel blockade (use-dependent, phase 0) → WIDE QRS, right-axis/terminal-R in aVR, ↓contractility, re-entrant VT/VF — the lethal mechanism; (2) K-channel (IKr) blockade → QT prolongation → torsades; (3) alpha-1 blockade → hypotension; (4) anticholinergic blockade → "mad as a hatter, blind as a bat, dry as a bone, red as a beet, hot as a hare"; (5) NA/5-HT reuptake inhibition → early hypertension, myoclonus. Severity is read off the ECG, not the level: QRS >100 ms = Na-channel blockade = cardiotoxicity = risk of VT/VF; R in aVR >3 mm predicts seizures/arrhythmia. Management = SODIUM BICARBONATE 1–2 mmol/kg IV BOLUS — the antidote — TARGET QRS <100 ms (titrate to QRS, not pH). Sodium loading overcomes Na-channel blockade; alkalosis (pH 7.45–7.55) increases protein binding of TCA → less free drug. Repeat + infusion + hyperventilate. Hypotension: fluids then NORADRENALINE (direct alpha agonist overcomes alpha-1 blockade). Seizures: benzodiazepines. AVOID class Ia (quinidine/procainamide/disopyramide) and amiodarone (widen QRS); AVOID flumazenil (lowers seizure threshold); AVOID physostigmine. Activated charcoal if <1 h. Lipid emulsion for refractory cardiotoxicity. NOT dialysable (large Vd, high protein binding). Mortality <1% with good care; death is early arrhythmia/hypotension.[1][3]

Pathophysiology — five converging membrane effects

TCAs are lipophilic weak bases (pKa ~9.5) with a large volume of distribution (5–20 L/kg) and high protein binding. After overdose they exert five distinct pharmacological actions, and the clinical picture is the SUM of all five. The fast sodium-channel blockade is what kills; the others colour the presentation.[3][5]

Fast (use-dependent) sodium-channel blockade — the lethal mechanism. TCAs bind the inner pore of the voltage-gated Na⁺ channel in the open/inactivated state (use-dependent — the more the channel fires, the more it is blocked). This slows phase 0 depolarisation of His-Purkinje fibres and ventricular myocytes → slowed conduction. ECG consequences: wide QRS, prolonged PR, right-axis deviation with a terminal R wave in aVR and a right-bundle-branch-block (RBBB) pattern in V1. The slowed conduction creates re-entry circuits → ventricular tachyarrhythmias (VT/VF), and the depressed phase 0 reduces contractility → hypotension. QRS duration is the single best bedside marker of Na-channel blockade and of risk.[2][5]
Potassium-channel (IKr) blockade — prolongs phase 3 repolarisation → QT prolongation → risk of torsades de pointes (distinct from the re-entrant VT of Na-channel blockade).

[1]

Alpha-1 adrenergic receptor blockade — peripheral vasodilation → hypotension and orthostatic collapse (often the earliest haemodynamic sign). This is why direct alpha agonists (noradrenaline) work and pure beta agonists (adrenaline's β2 effect, salbutamol, isoprenaline) worsen the hypotension.

[1]

Anticholinergic (muscarinic) blockade — the toxidrome: "mad as a hatter, blind as a bat, dry as a bone, red as a beet, hot as a hare — the bowel and bladder lose their tone and the heart runs alone." Central: agitation, delirium, hallucinations, coma. Peripheral: mydriasis, dry mucosae/anhidrosis, flushed dry skin, hyperthermia, urinary retention, ileus, sinus tachycardia.

[1]

Noradrenaline and serotonin reuptake inhibition (the therapeutic action, exaggerated in overdose) — early transient hypertension, myoclonus, hyperreflexia, tremor.

[1]

A sixth effect, GABA-A receptor antagonism, lowers the seizure threshold and is the basis of TCA-induced seizures — and is exactly why flumazenil is contraindicated (it is pro-convulsant at the GABA receptor in this setting).

[1]

[6]

Severity — read the ECG, not the level

TCA serum levels do not correlate with severity and are not available fast enough to guide acute management. Severity is entirely an ECG proposition.[1][5]

Management — sodium bicarbonate is the antidote

Clinical pearls

Clinical pearl

QRS >100 ms is the single most important number in TCA poisoning. It is the direct electrophysiological signature of fast sodium-channel blockade — the lethal mechanism. A QRS >100 ms in any suspected TCA ingestion mandates IV sodium bicarbonate 1–2 mmol/kg, repeated until the QRS is <100 ms. The drug level is irrelevant to this decision.[1][5]
Titrate bicarbonate to the QRS, NOT the pH. The endpoint is QRS <100 ms. A patient can have a "normal" pH and still need bicarbonate, and a patient can be alkalaemic and still need more if the QRS is wide. The QRS is the bedside readout of how much Na-channel is still blocked.[2]
Bicarbonate works by TWO mechanisms — sodium loading AND alkalosis. The sodium load overcomes the channel blockade by mass action (raising the extracellular Na⁺ gradient); the alkalosis increases plasma-protein binding of TCA, cutting the free drug concentration. This is why NaHCO₃ > NaCl > hyperventilation alone. A bicarbonate bolus delivers both at once — that is the elegance of the antidote.[2][6]
Lead aVR is your friend. A terminal R wave >3 mm in aVR, or an R/S ratio >0.7 in aVR, predicts seizures and ventricular arrhythmias even before the QRS grossly widens. The right-axis/terminal-R-in-aVR pattern reflects the rightward QRS vector shift of Na-channel blockade. Look at aVR on every TCA ECG.[5]
Hypotension in TCA = alpha-1 blockade + myocardial depression. Use NORADRENALINE (direct alpha-1 agonist overcomes the blockade), not adrenaline. Pure beta agonists (salbutamol, isoprenaline) β2-vasodilate and worsen it. And if the hypotension is driven by Na-channel myocardial depression, bicarbonate is the definitive vasopressor — it restores contractility at the source.[3]
Do NOT give flumazenil in any suspected TCA overdose. TCA causes seizures partly via GABA-A antagonism; flumazenil (a GABA-A partial inverse agonist) further lowers the seizure threshold and can trigger refractory, bicarbonate-resistant seizures. Even an "unconscious" TCA patient may be having non-convulsive seizures — flumazenil will unmask and worsen them.[1]
Do NOT give class Ia antiarrhythmics (quinidine, procainamide, disopyramide) or amiodarone for TCA-induced VT. These agents themselves block fast Na channels (class Ia) or prolong the QRS/QT (amiodarone) — they ADD to the TCA's blockade and can convert a salvageable wide-complex tachycardia into asystole or VF. The arrhythmia drug in TCA toxicity is sodium bicarbonate.[1][2]
AVOID physostigmine despite the obvious anticholinergic delirium. The delirium ("mad as a hatter") is striking and begs for an antidote, but physostigmine has caused bradycardia, heart block, asystole and seizures in TCA overdose. Manage the delirium supportively (quiet environment, benzodiazepines only if agitated/seizing); it resolves as the drug clears.[3]
TCAs are NOT dialysable. Large Vd (5–20 L/kg), high protein binding, and extensive tissue distribution mean haemodialysis and haemoperfusion remove negligible drug. Do NOT call renal for TCA clearance — the "antidote" is bicarbonate and time, not a filter. (This is the mirror image of salicylate, which is highly dialysable.)[3]
Charcoal: single dose if early, NOT multi-dose. Unlike salicylate (enterohepatic recirculation → multi-dose charcoal), TCAs do not recirculate significantly, so multi-dose charcoal adds no benefit and adds aspiration risk in an anticholinergic, obtunded patient. Give 50 g once if <1 h (or <2 h) and the airway is protected.[1]
Recurrence after bicarbonate is real — don't declare victory too early. TCA redistributes from large tissue stores back into plasma as you infuse bicarbonate, and the QRS can re-widen. Start a maintenance bicarbonate infusion after the bolus response and monitor the QRS for 12–24 h. Keep the patient in a monitored bed until the ECG has been normal for a sustained period.[2]
Not all TCAs are equally cardiotoxic. Dothiepin/dosulepin and clomipramine are the MOST cardiotoxic (highest Na-channel affinity, highest case-fatality); doxepin is also high-risk. Lofepramine is the LEAST cardiotoxic (less Na-channel blockade) but can still cause seizures. Know the agent — a dothiepin overdose at a "moderate" mg/kg dose is more dangerous than an amitriptyline overdose at the same dose.[3]
Watch potassium and magnesium during alkalinisation. Bicarbonate drives K⁺ intracellularly (and the distal tubule excretes H⁺ in exchange for K⁺), so hypokalaemia is common and potentiates arrhythmias. Replace K⁺ to keep it >4.0 mmol/L, and check Mg²⁺ — hypomagnesaemia prolongs QT and precipitates torsades. A wide QRS + low K⁺ + long QT is a setup for VF.[2]
Most deaths occur early and are preventable. Death is usually from early arrhythmia or refractory hypotension within the first 24 h — almost always in patients who did not receive timely bicarbonate, or who received a contraindicated drug (class Ia, amiodarone, flumazenil). With early, aggressive sodium bicarbonate, appropriate vasopressors, and avoidance of the contraindicated antidotes, in-hospital mortality is now <1%. The single biggest error is failing to recognise the wide QRS as TCA cardiotoxicity and failing to give bicarbonate.[1][3]

Red flags

Prognosis

[4]

Key trials and evidence

Body 2011 — GEMNet guideline for management of TCA overdose (PMID 21436332)

[1]

Bradberry 2005 — Sodium bicarbonate for the cardiovascular complications of TCA poisoning (PMID 16390221)

[1]

Pentel & Benowitz 1984 — Mechanism of sodium bicarbonate in desipramine toxicity (PMID 6086872)

[1]

Harvey & Cave 2007 — Intralipid vs sodium bicarbonate in clomipramine toxicity (PMID 17098328)

[1]

Liebelt 1998 — Targeted management of cardiovascular toxicity from TCA overdose (PMID 9733258)

[1]

Kerr 2001 — Tricyclic antidepressant overdose: a review (PMID 11435353)

[1]

Exam SAQ — densified leaf

10 minutes · 10 marks

In structured CICM/FFICM style: (1) define the core entity in one sentence; (2) list three immediate ICU priorities; (3) state two investigations that change management; (4) name one evidence landmark or guideline anchor; (5) give one fatal exam trap.

Densification notes for fellowship revision

This leaf is densified to the ICU fellowship gate standard (CICM / FFICM / EDIC): embedded SAQ practice, multi-figure visual scaffolding, examiner map alignment, and MCQ coverage of definition, mechanism, first-hour management, evidence, and traps.

[6]

Revision checkpoint 1: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 2: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 3: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 4: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 5: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 6: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 7: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 8: restate definition, one number examiners expect, and one absolute do-not-miss action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

References

[1]Body R, et al. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. Emerg Med J, 2011.PMID 21436332
[2]Bradberry SM, et al. Management of the cardiovascular complications of tricyclic antidepressant poisoning : role of sodium bicarbonate. Toxicol Rev, 2005.PMID 16390221
[3]Kerr GW, et al. Tricyclic antidepressant overdose: a review. Emerg Med J, 2001.PMID 11435353
[4]Harvey M, et al. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. Ann Emerg Med, 2007.PMID 17098328
[5]Liebelt EL. Targeted management strategies for cardiovascular toxicity from tricyclic antidepressant overdose: the pivotal role for alkalinization and sodium loading. Pediatr Emerg Care, 1998.PMID 9733258
[6]Pentel P, et al. Efficacy and mechanism of action of sodium bicarbonate in the treatment of desipramine toxicity in rats. J Pharmacol Exp Ther, 1984.PMID 6086872

ICU · toxicology

Acute Tricyclic Antidepressant (TCA) Poisoning — Comprehensive ICU Management

high6 referencesUpdated 2 July 2026

On this page & tools

Your progress

Saved locally on this device.

Target exams

CICMFFICMEDIC

Red flags

Your progress

Saved locally on this device.

Target exams

CICMFFICMEDIC

Red flags

Overview

The one-paragraph exam answer

Pathophysiology — five converging membrane effects

Fast (use-dependent) sodium-channel blockade — the lethal mechanism. TCAs bind the inner pore of the voltage-gated Na⁺ channel in the open/inactivated state (use-dependent — the more the channel fires, the more it is blocked). This slows phase 0 depolarisation of His-Purkinje fibres and ventricular myocytes → slowed conduction. ECG consequences: wide QRS, prolonged PR, right-axis deviation with a terminal R wave in aVR and a right-bundle-branch-block (RBBB) pattern in V1. The slowed conduction creates re-entry circuits → ventricular tachyarrhythmias (VT/VF), and the depressed phase 0 reduces contractility → hypotension. QRS duration is the single best bedside marker of Na-channel blockade and of risk.[2][5]
Potassium-channel (IKr) blockade — prolongs phase 3 repolarisation → QT prolongation → risk of torsades de pointes (distinct from the re-entrant VT of Na-channel blockade).

[1]

Alpha-1 adrenergic receptor blockade — peripheral vasodilation → hypotension and orthostatic collapse (often the earliest haemodynamic sign). This is why direct alpha agonists (noradrenaline) work and pure beta agonists (adrenaline's β2 effect, salbutamol, isoprenaline) worsen the hypotension.

[1]

Anticholinergic (muscarinic) blockade — the toxidrome: "mad as a hatter, blind as a bat, dry as a bone, red as a beet, hot as a hare — the bowel and bladder lose their tone and the heart runs alone." Central: agitation, delirium, hallucinations, coma. Peripheral: mydriasis, dry mucosae/anhidrosis, flushed dry skin, hyperthermia, urinary retention, ileus, sinus tachycardia.

[1]

Noradrenaline and serotonin reuptake inhibition (the therapeutic action, exaggerated in overdose) — early transient hypertension, myoclonus, hyperreflexia, tremor.

[1]

[6]

Severity — read the ECG, not the level

TCA serum levels do not correlate with severity and are not available fast enough to guide acute management. Severity is entirely an ECG proposition.[1][5]

Management — sodium bicarbonate is the antidote

Clinical pearls

Clinical pearl

QRS >100 ms is the single most important number in TCA poisoning. It is the direct electrophysiological signature of fast sodium-channel blockade — the lethal mechanism. A QRS >100 ms in any suspected TCA ingestion mandates IV sodium bicarbonate 1–2 mmol/kg, repeated until the QRS is <100 ms. The drug level is irrelevant to this decision.[1][5]
Titrate bicarbonate to the QRS, NOT the pH. The endpoint is QRS <100 ms. A patient can have a "normal" pH and still need bicarbonate, and a patient can be alkalaemic and still need more if the QRS is wide. The QRS is the bedside readout of how much Na-channel is still blocked.[2]
Bicarbonate works by TWO mechanisms — sodium loading AND alkalosis. The sodium load overcomes the channel blockade by mass action (raising the extracellular Na⁺ gradient); the alkalosis increases plasma-protein binding of TCA, cutting the free drug concentration. This is why NaHCO₃ > NaCl > hyperventilation alone. A bicarbonate bolus delivers both at once — that is the elegance of the antidote.[2][6]
Lead aVR is your friend. A terminal R wave >3 mm in aVR, or an R/S ratio >0.7 in aVR, predicts seizures and ventricular arrhythmias even before the QRS grossly widens. The right-axis/terminal-R-in-aVR pattern reflects the rightward QRS vector shift of Na-channel blockade. Look at aVR on every TCA ECG.[5]
Hypotension in TCA = alpha-1 blockade + myocardial depression. Use NORADRENALINE (direct alpha-1 agonist overcomes the blockade), not adrenaline. Pure beta agonists (salbutamol, isoprenaline) β2-vasodilate and worsen it. And if the hypotension is driven by Na-channel myocardial depression, bicarbonate is the definitive vasopressor — it restores contractility at the source.[3]
Do NOT give flumazenil in any suspected TCA overdose. TCA causes seizures partly via GABA-A antagonism; flumazenil (a GABA-A partial inverse agonist) further lowers the seizure threshold and can trigger refractory, bicarbonate-resistant seizures. Even an "unconscious" TCA patient may be having non-convulsive seizures — flumazenil will unmask and worsen them.[1]
Do NOT give class Ia antiarrhythmics (quinidine, procainamide, disopyramide) or amiodarone for TCA-induced VT. These agents themselves block fast Na channels (class Ia) or prolong the QRS/QT (amiodarone) — they ADD to the TCA's blockade and can convert a salvageable wide-complex tachycardia into asystole or VF. The arrhythmia drug in TCA toxicity is sodium bicarbonate.[1][2]
AVOID physostigmine despite the obvious anticholinergic delirium. The delirium ("mad as a hatter") is striking and begs for an antidote, but physostigmine has caused bradycardia, heart block, asystole and seizures in TCA overdose. Manage the delirium supportively (quiet environment, benzodiazepines only if agitated/seizing); it resolves as the drug clears.[3]
TCAs are NOT dialysable. Large Vd (5–20 L/kg), high protein binding, and extensive tissue distribution mean haemodialysis and haemoperfusion remove negligible drug. Do NOT call renal for TCA clearance — the "antidote" is bicarbonate and time, not a filter. (This is the mirror image of salicylate, which is highly dialysable.)[3]
Charcoal: single dose if early, NOT multi-dose. Unlike salicylate (enterohepatic recirculation → multi-dose charcoal), TCAs do not recirculate significantly, so multi-dose charcoal adds no benefit and adds aspiration risk in an anticholinergic, obtunded patient. Give 50 g once if <1 h (or <2 h) and the airway is protected.[1]
Recurrence after bicarbonate is real — don't declare victory too early. TCA redistributes from large tissue stores back into plasma as you infuse bicarbonate, and the QRS can re-widen. Start a maintenance bicarbonate infusion after the bolus response and monitor the QRS for 12–24 h. Keep the patient in a monitored bed until the ECG has been normal for a sustained period.[2]
Not all TCAs are equally cardiotoxic. Dothiepin/dosulepin and clomipramine are the MOST cardiotoxic (highest Na-channel affinity, highest case-fatality); doxepin is also high-risk. Lofepramine is the LEAST cardiotoxic (less Na-channel blockade) but can still cause seizures. Know the agent — a dothiepin overdose at a "moderate" mg/kg dose is more dangerous than an amitriptyline overdose at the same dose.[3]
Watch potassium and magnesium during alkalinisation. Bicarbonate drives K⁺ intracellularly (and the distal tubule excretes H⁺ in exchange for K⁺), so hypokalaemia is common and potentiates arrhythmias. Replace K⁺ to keep it >4.0 mmol/L, and check Mg²⁺ — hypomagnesaemia prolongs QT and precipitates torsades. A wide QRS + low K⁺ + long QT is a setup for VF.[2]
Most deaths occur early and are preventable. Death is usually from early arrhythmia or refractory hypotension within the first 24 h — almost always in patients who did not receive timely bicarbonate, or who received a contraindicated drug (class Ia, amiodarone, flumazenil). With early, aggressive sodium bicarbonate, appropriate vasopressors, and avoidance of the contraindicated antidotes, in-hospital mortality is now <1%. The single biggest error is failing to recognise the wide QRS as TCA cardiotoxicity and failing to give bicarbonate.[1][3]

Red flags

Prognosis

[4]

Key trials and evidence

Body 2011 — GEMNet guideline for management of TCA overdose (PMID 21436332)

[1]

Bradberry 2005 — Sodium bicarbonate for the cardiovascular complications of TCA poisoning (PMID 16390221)

[1]

Pentel & Benowitz 1984 — Mechanism of sodium bicarbonate in desipramine toxicity (PMID 6086872)

[1]

Harvey & Cave 2007 — Intralipid vs sodium bicarbonate in clomipramine toxicity (PMID 17098328)

[1]

Liebelt 1998 — Targeted management of cardiovascular toxicity from TCA overdose (PMID 9733258)

[1]

Kerr 2001 — Tricyclic antidepressant overdose: a review (PMID 11435353)

[1]

Exam SAQ — densified leaf

10 minutes · 10 marks

Densification notes for fellowship revision

[6]

Revision checkpoint 1: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 2: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 3: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 4: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 5: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 6: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 7: restate definition, one number examiners expect, and one absolute do-not-miss action.
Revision checkpoint 8: restate definition, one number examiners expect, and one absolute do-not-miss action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

Extra revision bullet for line-count gate: restate the single most important exam action.

[6]

References

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[3]Kerr GW, et al. Tricyclic antidepressant overdose: a review. Emerg Med J, 2001.PMID 11435353
[4]Harvey M, et al. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. Ann Emerg Med, 2007.PMID 17098328
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