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)
Sodium Channel Blocking Effects
The two main adverse effects of sodium-channel blocker poisoning include:
- 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
- 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.
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.
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.
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.
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.
- 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.
Another example of flecainide cardiotoxicity.
- 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
- 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