Toxicology & Substance Use · Topic 6 of 17

Tricyclic & Sodium-Channel Blocker Toxicity

Toxicology · sodium-channel blockers

Tricyclic & Sodium-Channel Blocker Toxicity

A QRS over 100 ms after a tricyclic overdose means sodium-channel blockade: push sodium bicarbonate and alkalinize to pH 7.45–7.55.

Key numbers

QRS over 100 ms predicts seizuresQRS > 100 ms

Sodium bicarbonate 1–2 mEq/kg IV push1–2 mEq/kg IV

Alkalinize to serum pH 7.45–7.55pH 7.45–7.55

Asymptomatic with normal ECG at 6 hoursobserve ≥ 6 h

01 · Defined byQRS over 100 ms predicts seizures

In TCA overdose the ECG, not the drug level, stratifies risk: QRS > 100 ms predicts seizures (about one-third) and QRS > 160 ms predicts ventricular arrhythmias (about half).

02 · GiveSodium bicarbonate 1–2 mEq/kg IV push

Give sodium bicarbonate 1–2 mEq/kg IV push for QRS > 100 ms, ventricular dysrhythmia or fluid-refractory hypotension; repeat boluses until the QRS narrows and blood pressure recovers.

03 · The numberAlkalinize to serum pH 7.45–7.55

After the boluses, run an infusion (150 mEq sodium bicarbonate in 1 L D5W) titrated to a serum pH of 7.45–7.55, checking blood gases; continue until the QRS normalizes.

What it is

Core idea

Four toxic actions: Na⁺ block, anticholinergic, α₁, GABATCAs block fast sodium channels (wide QRS, ventricular dysrhythmias), muscarinic receptors (anticholinergic toxidrome), α₁ receptors (vasodilation, hypotension) and GABA-A receptors (seizures).

Presentation

What you'll see

Terminal R wave in aVR over 3 mmSodium-channel blockade on the ECG: QRS widening, a terminal R wave in aVR > 3 mm (terminal rightward axis), Brugada-like pattern and wide-complex tachycardia; anticholinergic sinus tachycardia is common.

Anticholinergic toxidrome, then rapid deteriorationEarly anticholinergic signs (tachycardia, mydriasis, dry flushed skin, urinary retention, agitation or delirium) can progress quickly to coma, seizures, hypotension and ventricular dysrhythmias — never induce emesis.

Diagnosis & monitoring

Work-up

Asymptomatic with normal ECG at 6 hoursMonitor with serial ECGs; a patient who remains asymptomatic with a normal ECG (QRS < 100 ms) 6 hours after ingestion can be medically cleared, with psychiatric evaluation after an intentional overdose.

Watch potassium during bicarbonate therapyHypokalemia is the most common complication of sodium bicarbonate therapy; also watch for hypocalcemia, volume overload and excessive alkalosis.

Do right now

In this order

First moves

QRS over 100 ms predicts seizuresQRS > 100 ms

→

Sodium bicarbonate 1–2 mEq/kg IV push1–2 mEq/kg IV

→

Treat TCA seizures with a benzodiazepine

→

Hypotension: fluids, bicarbonate, then norepinephrine

Why each step

QRS over 100 ms predicts seizuresIn TCA overdose the ECG, not the drug level, stratifies risk: QRS > 100 ms predicts seizures (about one-third) and QRS > 160 ms predicts ventricular arrhythmias (about half).

Sodium bicarbonate 1–2 mEq/kg IV pushGive sodium bicarbonate 1–2 mEq/kg IV push for QRS > 100 ms, ventricular dysrhythmia or fluid-refractory hypotension; repeat boluses until the QRS narrows and blood pressure recovers.

Treat TCA seizures with a benzodiazepineTreat seizures with a benzodiazepine, then phenobarbital or propofol if refractory; seizures cause acidosis, which worsens sodium-channel cardiotoxicity, so give sodium bicarbonate as well.

Hypotension: fluids, bicarbonate, then norepinephrineTreat hypotension with isotonic fluid and sodium bicarbonate; if it persists, start a direct-acting vasopressor, norepinephrine first, which counters TCA α₁ blockade.

Management

Orders

Activated charcoal only with a protected airwayActivated charcoal (0.5–2 g/kg; about 50–100 g in adults) is reasonable within 1–2 hours in an alert patient with a protected airway; never induce emesis because the patient can deteriorate abruptly.

VA-ECMO or lipid emulsion for refractory toxicityFor cardiogenic shock refractory to bicarbonate and vasopressors, VA-ECMO is reasonable where available; 20% lipid emulsion (1.5 mL/kg, then 0.25 mL/kg/min) may be tried as a last resort, not first-line.

Red flags & don'ts

Avoid harm

Lidocaine second-line; avoid class IA/IC antiarrhythmics avoidFor ventricular dysrhythmias give sodium bicarbonate first; lidocaine (class Ib) is a reasonable second-line drug. Avoid class IA (procainamide, quinidine) and IC (flecainide) antiarrhythmics — they are sodium-channel blockers themselves.

Do not give flumazenil with a TCA co-ingestion avoidDo not give flumazenil when a TCA may be co-ingested: it can precipitate seizures and dysrhythmias, and AHA 2023 rates it harmful in patients at risk for either.

The rules

Know these

Dialysis does not remove tricyclicsExtracorporeal removal is not recommended in severe TCA poisoning (EXTRIP 1D): the drugs are highly protein-bound with a very large volume of distribution, so hemodialysis removes almost none.

More detail

Reference

Show 6 reference facts

Other sodium-channel blockers cause the same wide-QRS picture: class IA/IC antiarrhythmics, cocaine, diphenhydramine, carbamazepine, lamotrigine and venlafaxine. Bicarbonate may not narrow QRS widening from bupropion or propranolol.

Bicarbonate works two ways: the sodium load competes at the blocked channel, and alkalosis increases protein binding and lowers the free, active drug.

In an intubated patient who cannot take more sodium or volume, hyperventilation also alkalinizes; combined with bicarbonate it can cause profound alkalosis.

Serum TCA levels do not guide acute care — QRS duration predicts seizures and dysrhythmias better — and qualitative urine drug screens can give false-positive results, so the ECG drives management.

TCAs have a narrow margin of safety: a significant overdose is potentially lethal, which is a main reason they are now rarely prescribed for depression.

Poison-center guidance refers ingestions above 5 mg/kg of most TCAs (2.5 mg/kg for desipramine or nortriptyline) and every intentional or symptomatic ingestion to the emergency department.

Pearl

Treat the QRS, not the drug level: bicarbonate boluses until the complex narrows.

Sources · Merck Manual Professional — Symptoms and Treatment of Specific Poisons (tricyclic antidepressants) · Bruccoleri RE, Burns MM. A literature review of the use of sodium bicarbonate for the treatment of QRS widening. J Med Toxicol 2016;12:121–129 · Yates C et al. Extracorporeal treatment for tricyclic antidepressant poisoning: recommendations from the EXTRIP Workgroup. Semin Dial 2014;27:381–389 · Merck Manual Professional — Benzodiazepines and Barbiturates (flumazenil cautions) · Merck Manual Professional — General Principles of Poisoning · Merck Manual Professional — Medications for Treatment of Depression (heterocyclic antidepressants) · Lavonas EJ et al. 2023 AHA focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning. Circulation 2023;148:e149–e184 · Woolf AD et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management (AAPCC). Clin Toxicol 2007;45:203–233 (abstract via Europe PMC) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).