Key Facts

TCA overdose remains one of the most dangerous drug overdoses in the UK despite declining prescription rates. Rapid deterioration can occur, and early recognition of ECG changes is crucial for timely treatment.

Epidemiology

TCA prescriptions have decreased significantly with the rise of SSRIs, but TCAs remain in common use for neuropathic pain, migraine prophylaxis, and nocturnal enuresis. Amitriptyline and dosulepin account for the most toxic overdoses. Dosulepin is the most toxic TCA (highest fatality index).

Aetiology

• Intentional self-harm: Most common — often impulsive
• Accidental overdose: Children, medication errors in elderly
• TCAs prescribed for: Depression, neuropathic pain, migraine, fibromyalgia, IBS, nocturnal enuresis

Pathophysiology

TCAs exert toxicity through multiple mechanisms:

1. Sodium channel blockade: Slows phase 0 depolarisation → QRS widening → ventricular arrhythmias → cardiac arrest (sodium bicarbonate reverses this)
2. Anticholinergic (muscarinic) blockade: Tachycardia, dry mouth, dilated pupils, urinary retention, reduced gut motility
3. Alpha-1 adrenergic blockade: Vasodilation → hypotension
4. Potassium channel blockade: QTc prolongation → torsades de pointes
5. GABA-A receptor antagonism: Lowers seizure threshold
6. Noradrenaline/serotonin reuptake inhibition: Initial sympathetic stimulation

Clinical Features (Dose-Dependent)

Mild toxicity (5-10mg/kg):

• Anticholinergic features: Dry mouth, tachycardia, dilated pupils, drowsiness

Moderate toxicity (10-20mg/kg):

• Confusion, agitation, hallucinations
• Urinary retention, absent bowel sounds
• Sinus tachycardia, mild hypotension
• QRS prolongation beginning

Severe toxicity (>20mg/kg):

• Coma (GCS ≤8)
• Seizures (often generalised)
• QRS >160ms — risk of VT/VF
• Refractory hypotension
• Respiratory depression
• Hyperthermia

Red Flags

• QRS >120ms — administer sodium bicarbonate immediately
• QRS >160ms — high risk of life-threatening arrhythmia
• Seizures — benzodiazepines only (NOT phenytoin — worsens cardiac conduction)
• Rapid GCS deterioration — prepare for intubation
• Right axis deviation of terminal 40ms (R in aVR >3mm) — early sign of sodium channel blockade

Bedside

• 12-lead ECG: CRITICAL — assess QRS duration, QTc, terminal R wave in aVR, axis deviation; repeat every 30 min
• Continuous cardiac monitoring: Minimum 6 hours (some recommend 12h)
• Blood glucose: Exclude hypoglycaemia
• Temperature: Hyperthermia

Bloods

• ABG/VBG: pH (target alkalotic with bicarb); lactate
• Paracetamol level: Always check for co-ingestion
• U&Es: Electrolytes, renal function
• FBC, LFTs: Baseline
• CK: If prolonged seizures or hyperthermia (rhabdomyolysis)

Imaging

• CXR: If aspiration suspected
• CT head: If prolonged seizures or focal neurology

Special Tests

• TCA drug level: NOT routinely available; clinical features and ECG are more useful
• TOXBASE/NPIS: Consult for management guidance

Non-pharmacological

• Resuscitation area: All TCA overdoses — continuous cardiac monitoring
• Activated charcoal 50g PO: If within 1 hour of ingestion and airway protected
• Intubation: If GCS ≤8 or respiratory failure

Pharmacological

Sodium bicarbonate 8.4% IV:

• Indication: QRS >120ms, ventricular arrhythmias, hypotension
• Dose: 50mL (50mmol) IV bolus; repeat until QRS narrows
• Target pH: 7.45-7.55 (alkalosis enhances protein binding of TCA and reverses sodium channel blockade)
• Mechanism: Increases extracellular sodium (overcomes sodium channel blockade) and alkalosis increases drug protein binding

Seizures:

• Diazepam 10-20mg IV or lorazepam 4mg IV
• Do NOT use phenytoin (worsens cardiac conduction)
• Refractory seizures — propofol, thiopental; consider intubation

Hypotension:

• IV crystalloid fluid boluses
• Sodium bicarbonate (if QRS wide)
• Noradrenaline if fluid and bicarb unresponsive
• Avoid vasopressin (worsens arrhythmia risk)

Arrhythmias:

• VT: Sodium bicarbonate first; lidocaine 1mg/kg if refractory
• Do NOT use class Ia/Ic antiarrhythmics, beta-blockers, or calcium channel blockers
• Torsades de pointes: Magnesium 2g IV
• Refractory cardiac arrest: Intralipid 20% (1.5mL/kg bolus, then infusion)

Surgical/Interventional

• ECMO: Last resort for refractory cardiogenic shock
• Intralipid emulsion 20%: For cardiac arrest or refractory cardiovascular collapse

Referral Criteria

• QRS >120ms — resuscitation area, senior review
• Seizures, arrhythmias, or GCS ≤8 — ICU
• Cardiac arrest — full ALS + sodium bicarbonate + intralipid
• All intentional overdoses — psychiatric assessment

• Overall TCA overdose mortality: ~2-5%
• QRS >120ms: ~33% risk of seizures
• QRS >160ms: ~50% risk of ventricular arrhythmias
• If QRS normalises within 6 hours: Very low risk of subsequent arrhythmia
• Survivors: Full recovery expected if no prolonged cardiac arrest or hypoxic brain injury
• Dosulepin: Highest fatality index of all TCAs — 1 week's supply at therapeutic dose can be lethal

TCA ECG Changes (Sequential)

Management Summary