Tricyclic Overdose

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.

ECG TCA overdose Sodium Channel Blocking Agent Toxicity

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:
Dominant secondary R wave (R') in aVR
Dominant secondary R wave (R’) in aVR > 3mm

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
ECG TCA toxicity 1 2

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
ECG TCA toxicity 2 2

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
ECG TCA toxicity 3 resolution 2

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
ECG Massive TCA overdose sodium channel toxicity 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
ECG Flecainide toxicity 1 2

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
ECG Flecainide toxicity 3

Another example of flecainide cardiotoxicity.

Related Topics

LITFL Further Reading

Advanced Reading




Emergency Physician in Prehospital and Retrieval Medicine in Sydney, Australia. He has a passion for ECG interpretation and medical education | ECG Library |

One comment

  1. Hi Ed, fellow readers

    Great post! Thanks Ed & litfl!

    May I ask if there’s a rationale for diazepam over alternatives here?

    “Treat seizures with IV benzodiazepines (e.g. diazepam 5-10mg)”

    Midaz is more commonly used for seizure termination I’d have thought and my understanding is it had been shown to provide a longer ” seizure free” period vs. diazepam? I know a relatively recent trial showed IV lorazepam was best but I haven’t see this used in Australia.

    Just curious if suggesting diaz uses a rationale that the patient is already tubed and on M&M and thus try diazepam if still seizing? Or if they’re on propofol for sedation / regardless of sedation / when seizing occurs you suggest diazepam first line?


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