Tricyclic Antidepressants

Present with features of:

• Sodium channel blockade
  • Broad complex arrhythmia
• Anticholinergic toxicity
  • Tachycardia
  • Mydriasis
  • Dry mouth and skin
  • Urinary retention
• α₁-blockade
  • Hypotension
• ↓ Catecholamine reuptake
  • Initial ↑ sympathetic tone with hypertension
  • Secondary by prolonged ↓ sympathetic tone and hypotension

Epidemiology and Risk Factors

• Leading cause of death from overdose patients arriving alive at ED
• 50% of all ICU overdose admissions

Pathophysiology

Aetiology

Clinical Features

Assessment

History:

• Dose
  • 10mg/kg is potentially life threatening
  • 30mg/kg associated with pH dependent toxicity and coma for >24 hours
• Timing
  Asymptomatic window for up to 6 hours.

Exam:

Investigations

Bedside:

• ECG
  • Sodium channel blockade
    • PR prolongation
    • QRS >100ms
      Due to IV conduction delay. Risk of VT (and seizures) ↑ with ↑ QRS width.
    • Terminal R wave >3mm in aVR
      ↑ Susceptibility of the right IV conducting system to Na⁺-channel blockade, causing terminal right axis deviation.
  • Anticholinergic
    • Sinus tachycardia
  • Malignant arrhythmias

Laboratory:

Imaging:

Other:

Diagnostic Approach and DDx

Management

• Give activated charcoal
• Induce alkalosis with sodium bicarbonate
• Normalise physiology
  Hypothermia and hypotension all ↑ toxicity.
• Treat arrhythmias and seizures

Sodium bicarbonate is beneficial through a number of mechanisms:

• Alkalosis
  • ↑ Unionised portion of drug (pKa 8.4) ↓ free drug by:
    • Facilitating distribution into peripheral compartments
    • ↑ Protein binding
  • ↓ Binding of TCA to channel
  • Corrects any of the usual physiological detriments of acidosis
• Sodium
  • Directly antagonises Na⁺ channel blockade

Specific therapy:

• Pharmacological
  • Induce alkalosis: Target pH 7.5-7.55
    Indicated for ↑ QRS. Mechanisms include:
    • Sodium bicarbonate
      Preferable as ↑ Na⁺ overcomes Na⁺-channel blockade.
    • Hyperventilation
      Does not provide the benefits that sodium does, and undesirably ↓ CBF.
  • Activated charcoal
    Multi-dose.
• Procedural
• Physical

Supportive care:

• A
  • Intubation for airway protection
• C
  • Fluid resuscitation
  • Antiarrhythmics
    • Avoid class 1a agents as they worsen sodium channel blockade
    • Lignocaine preferable
• D
  • Seizure control
    May need intubation and propofol infusion.
• E
  • Normothermia

Disposition:

Preventative:

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

Prognosis

Key Studies

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References

1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.