Seizures, Somnolence and a Scary ECG

The ECG shows:

• Regular broad complex tachycardia
• Rate 130 bpm
• Right axis deviation (+120 degrees)
• Hidden P waves buried in the ST-segments / T waves (best seen in leads II, aVF). These could be retrograde P waves from a junctional / ventricular rhythm or sinus P waves with an extremely long PR interval (360ms)
• Very broad QRS complexes (160ms)
• Terminal R wave in aVR > 3mm; R/S ratio in aVR > 0.7
• Atypical RBBB pattern in V1-2 (bizarre morphology with left rabbit ear higher than the right)
• QT 400ms with markedly prolonged QTc 590 ms
• Non-specific T wave abnormalities with T-wave inversions in V1-2 & lead III

he combination of tachycardia, QRS and QTc prolongation, right axis deviation and terminal R wave in aVR > 3mm is highly specific for poisoning with sodium-channel blocking drugs, in particular the tricyclic antidepressants.

This patient had attempted suicide by deliberate self-poisoning with around 35mg/kg of Doxepin (a tricyclic antidepressant) an hour prior to presentation.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)

The risk assessment for Doxepin ingestion is as follows:

• < 5 mg/kg — Minimal symptoms
• 5-10 mg / kg — Drowsiness and mild anticholinergic effects; major toxicity not expected
• > 10 mg / kg — Potential for all major toxic effects to occur within 1-2 h of ingestion
• > 30 mg / kg — Severe toxicity with pH-dependent cardiotoxicity and coma > 24 h

An overdose of this magnitude (> 30 mg/kg) is associated with profound TCA toxicity and likely to be rapidly fatal without intervention.

Management:

• This patient needs 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 further 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 second line agent 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.

LITFL: Toxicology Conundrum 022 – Tricyclic antidepressant (TCA) toxicity.