Sodium Channel Blocking Agent Toxicity

The ECG is a vital tool in the prompt diagnosis of poisoning with sodium-channel blocking medications such as tricyclic antidepressant (TCA) overdose.

Sodium Channel Blocking Medications

• Tricyclic antidepressants (= most common)
• Type Ia antiarrhythmics (quinidine, procainamide)
• Type Ic antiarrhythmics (flecainide, encainide)
• Local anaesthetics (bupivacaine, ropivacaine)
• Antimalarials (chloroquine, hydroxychloroquine)
• Dextropropoxyphene
• Propranolol
• Carbamazepine
• Quinine

Sodium Channel Blocking Effects

The two main adverse effects of sodium-channel blocker poisoning include:

• Seizures
• Ventricular dysrhythmias (due to blockade of sodium channels in the CNS and myocardium)

Handy tip: An ECG should be taken in all patients who present with a deliberate self-poisoning (or altered GCS of unknown aetiology) to screen for TCA overdose.

ECG Features of Sodium-Channel Blockade

Features consistent with sodium-channel blockade:

• Interventricular conduction delay — QRS > 100 ms in lead II
• Right axis deviation of the terminal QRS:
  • Terminal R wave > 3 mm in aVR
  • R/S ratio > 0.7 in aVR
• Patients with tricyclic overdose will also usually demonstrate sinus tachycardia secondary to muscarinic (M1) receptor blockade.

Clinical Features of Tricyclic Overdose

In overdose, the tricyclics produce rapid onset (within 1-2 hours) of:

• Sedation and coma
• Seizures
• Hypotension
• Tachycardia
• Broad complex dysrhythmias
• Anticholinergic syndrome

Tricyclics mediate their cardiotoxic effects via blockade of myocardial fast sodium channels (QRS prolongation, tall R wave in aVR), inhibition of potassium channels (QTc prolongation) and direct myocardial depression.

Other toxic effects are produced by blockade at muscarinic (M1), histamine (H1) and α₁-adenergic receptors. The degree of QRS broadening on the ECG is correlated with adverse events:

• QRS > 100 ms is predictive of seizures
• QRS > 160 ms is predictive of ventricular arrhythmias (e.g. VT)

Management of Significant Tricyclic Overdose 

Overdose >10mg/kg with Signs of cardiotoxicity (ECG changes)

• Patients need to be managed in a monitored area equipped for airway management and resuscitation.
• Secure IV access, administer high flow oxygen and attach monitoring equipment.
• Administer IV sodium bicarbonate 100 mEq (1-2 mEq / kg); repeat every few minutes until BP improves and QRS complexes begin to narrow.
• Intubate as soon as possible.
• Hyperventilate to maintain a pH of 7.50 – 7.55.
• Once the airway is secure, place a nasogastric tube and give 50g (1g/kg) of activated charcoal.
• Treat seizures with IV benzodiazepines (e.g. diazepam 5-10mg).
• Treat hypotension with a crystalloid bolus (10-20 mL/kg). If this is unsuccessful in restoring BP then consider starting vasopressors (e.g. noradrenaline infusion).
• If arrhythmias occur, the first step is to give more sodium bicarbonate. Lidocaine (1.5mg/kg) IV is a third-line agent (after bicarbonate and hyperventilation) once pH is > 7.5.
• Avoid Ia (procainamide) and Ic (flecainide) antiarrhythmics, beta-blockers and amiodarone as they may worsen hypotension and conduction abnormalities.
• Admit the patient to the intensive care unit for ongoing management.

ECG Examples

Example 1a

Typical ECG of TCA toxicity demonstrating:

• Sinus tachycardia with first-degree AV block (P waves hidden in the T waves, best seen in V1-2).
• Broad QRS complexes.
• Positive R’ wave in aVR.

Example 1b

Delayed ECG with worsening TCA toxicity

A second ECG of the same patient showing worsening TCA cardiotoxicity with marked QRS broadening producing a sine wave appearance reminiscent of hyperkalaemia.

Example 1c

Resolution of TCA toxicity with treatment (bicarbonate and hyperventilation)

• Third ECG of the same patient after serum alkalinisation with sodium bicarbonate, intubation and hyperventilation.
• The QRS duration has narrowed back to normal and the R’ wave in aVR has disappeared.

Example 2

Massive TCA overdose

• Another example of severe TCA cardiotoxicity after ingestion of 35 mg/kg doxepin.
• There is marked QRS widening with tachycardia and a positive R’ wave in aVR.

Example 3

Flecainide overdose

• Similar ECG changes are seen with other sodium-channel blocking agents.
• This ECG demonstrates QRS widening and positive R’ wave in aVR consistent with sodium-channel blockade in a patient with flecainide poisoning.

Example 4

Another example of flecainide cardiotoxicity.

Related Topics

• LITFL Tricyclic Antidepressant TCA Overview – TOX Library
• LITFL Toxicology Conundrum 022
• LITFL Toxicology Conundrum 050

LITFL Further Reading

• ECG Library Basics – Waves, Intervals, Segments and Clinical Interpretation
• ECG A to Z by diagnosis – ECG interpretation in clinical context
• ECG Exigency and Cardiovascular Curveball – ECG Clinical Cases
• 100 ECG Quiz – Self-assessment tool for examination practice
• ECG Reference SITES and BOOKS – the best of the rest

Advanced Reading

• Brady WJ, Truwit JD. Critical Decisions in Emergency and Acute Care Electrocardiography
• Surawicz B, Knilans T. Chou’s Electrocardiography in Clinical Practice: Adult and Pediatric
• Wagner GS. Marriott’s Practical Electrocardiography 12e
• Chan TC. ECG in Emergency Medicine and Acute Care
• Rawshani A. Clinical ECG Interpretation
• Mattu A. ECG’s for the Emergency Physician
• Hampton JR. The ECG In Practice, 6e