Tricyclic and Sodium Channel Blocker Toxicity

In the His-Purkinje system and myocardium, tricyclic antidepressants (TCAs) and other sodium channel blockers slow phase 0 depolarization. The result is QRS widening and conduction delay. The patient is at risk of ventricular dysrhythmia. TCAs also block central muscarinic and histamine receptors, alpha-adrenergic receptors and GABA-A receptors. That blockade adds anticholinergic signs, hypotension and seizures.

• Agents: TCAs (amitriptyline, nortriptyline, imipramine, clomipramine), cyclobenzaprine, class Ia and Ic antiarrhythmics, diphenhydramine, carbamazepine, bupropion, hydroxychloroquine, chloroquine, quinine, local anesthetics such as lidocaine and bupivacaine, and cocaine.
• Course: Toxicity usually begins within 1–2 hours of ingestion. It can progress quickly. The serum drug level correlates poorly with toxicity. At the bedside, the QRS is the marker.

Typical Presentation

• Early: sinus tachycardia, dry mucosa, mydriasis, urinary retention, agitation or drowsiness.
• Severe: hypotension, wide-complex rhythm, seizure, coma or respiratory depression.

Red Flags

• QRS 100 ms or longer: tied to seizures in the 1985 Boehnert and Lovejoy study of TCA overdose (maximal limb-lead QRS). Read it as a risk marker, not a diagnostic cut-off.
• QRS 160 ms or longer: tied to ventricular dysrhythmias in the same study.
• Any seizure, coma or hypotension after a suspected ingestion.

See Toxicology Panel and Bicarbonate. For the QRS, see QRS Complex.

• Other wide-complex tachycardias: ventricular tachycardia and hyperkalemia are on the list too. The sodium channel blocker history and anticholinergic signs separate them. See Wide Complex Tachycardia.
• Serotonin toxicity or anticholinergic toxidrome: Hyperthermia and clonus are the clues that point to serotonin syndrome. See Toxidromes.
• Sepsis or hypoglycemia: don't blame the coma or the shock on the drug alone until you've checked glucose and temperature.

1. Scene safety and history: ask about the agent, amount and time of ingestion, and whether other drugs were taken.
2. Airway and ventilation: support breathing and oxygenate. Assist ventilation early if the patient is drowsy or seizing.
3. Positioning and seizure precautions: protect the airway during a seizure. Do not restrain.
4. Notify early: request ALS and a transport decision as soon as sodium channel blocker toxicity is suspected.

Doses vary by protocol; follow local protocols and medical direction.

• Monitor and 12-lead ECG (Paramedic/RN/CCT): measure the QRS on every repeat ECG.
• IV or IO access (Paramedic/RN/CCT): see IO Access.
• Sodium bicarbonate (Paramedic/RN/CCT): 1–2 mEq/kg IV/IO bolus for QRS widening, ventricular dysrhythmia or hypotension, using the 8.4% (1 mEq/mL) product in adults and older children (infants: see Special Populations). Repeat to narrow the QRS and stop at pH 7.55 (sodium bicarbonate page: Sodium Bicarbonate). Repeat the ECG and pH after each bolus. The bicarbonate label's cardiac-arrest dosing repeats every 5 to 10 minutes guided by blood gas; the interval for this toxicity is per protocol.
• Seizure (Paramedic/RN/CCT): benzodiazepine per protocol, such as midazolam or diazepam. Treat early: seizures add lactic acidosis and hypoxia, which worsen the QRS and rhythm. If seizures persist, escalate per toxicology or medical direction (barbiturate or propofol with airway control). Avoid phenytoin and fosphenytoin, which add sodium channel blockade.
• Ventricular dysrhythmia: treat as a sodium channel blocker dysrhythmia first, with bicarbonate; defibrillation and ACLS per protocol. Avoid class Ia and Ic antiarrhythmics (procainamide, flecainide). Any other antiarrhythmic is a toxicology or medical-direction decision.
• Hypotension (Paramedic/RN/CCT): sodium bicarbonate first, then a modest fluid bolus with reassessment, because TCA toxicity can depress myocardial function. If hypotension persists, start a vasopressor per protocol; norepinephrine is commonly used first. Consider early toxicology and ECMO consultation for refractory shock.
• Airway (Paramedic/RN/CCT): intubate early for airway protection, hypoventilation or refractory seizure. After intubation, match minute ventilation to the patient's pre-intubation effort; hypoventilation raises PaCO₂ and worsens acidosis. See Intubation.

• Bicarbonate endpoint: serial ECGs and gases, aiming for a pH of 7.50–7.55 and a narrowing QRS. Track serum sodium, potassium and ionized calcium with each bolus. The bicarbonate label warns of rising plasma sodium, fluid and solute overload, and potassium depletion or hypocalcemia as pH rises. Stop or reduce bicarbonate at the sodium limit set by local protocol.
• Lipid emulsion: for local anesthetic systemic toxicity with a life-threatening wide-complex rhythm, per local protocol. The ASRA LAST checklist is the reference for LAST management. It is not a standard TCA treatment.
• Refractory cases: escalate to a toxicologist and the ICU. Save ECMO for refractory cases, per local protocol.
• Avoid: flumazenil (seizure risk in mixed cyclic antidepressant overdose), physostigmine (asystole, seizures, bradycardia), and class Ia and Ic antiarrhythmics (procainamide, flecainide).

• Destination: an ICU-capable hospital with toxicology access. Call the poison center early.
• Monitor in transit: continuous ECG and SpO₂ the whole way. Watch the QRS and rhythm. Keep monitoring even when the patient looks stable.
• Drugs to carry: sodium bicarbonate, a benzodiazepine, and airway equipment. Confirm local stocking.
• Handoff: agent, amount and time; QRS at each ECG; bicarbonate total given; seizure history; last pH.

• Pediatrics: sodium bicarbonate 1–2 mEq/kg IV/IO bolus, weight-based. See Weight-Based Dosing. In infants and neonates, the label says a 4.2% (0.5 mEq/mL) solution may be preferred, or use a dilution, given slowly. The 8.4% label warns that rapid hypertonic injection into children under two can cause hypernatremia, lower CSF pressure and intracranial hemorrhage. The label also says 4.2% may be preferred. A reported TCA ingestion in a child counts as significant, so call the poison center early. Lipid emulsion for pediatric local anesthetic toxicity: see the pediatric systematic review in References.
• Pregnancy: Treat the maternal toxicity first. This page does not set bicarbonate or benzodiazepine dosing in pregnancy. Follow protocol and get obstetric input early.
• Older Adults: No specific adjustment is established. Age-related cardiac disease raises the risk of dysrhythmia.
• Patients on Beta-Blockers or Calcium Channel Blockers: Together they stack bradycardia and hypotension. See Adult Bradycardia.

• Error: Treating the drug level like the target. It isn't. The QRS is. Measure it and act on what it shows.
• Error: Calling it done at the first narrow QRS. One good ECG is a pause, not the finish line. Keep repeating to hold the QRS narrow and the pH in range.
• Error: Reaching for flumazenil because the coma looks like benzodiazepines in a mixed overdose. It can cause seizures.
• Error: Hypoventilating during or after bicarbonate. After intubation, match minute ventilation to the patient's pre-intubation effort. Hypoventilation raises PaCO₂ and makes the acidosis worse. Hyperventilating will not replace bicarbonate.