FRCA Notes

Tricyclic Antidepressant Overdose

Resources

  • The toxicology of TCA overdose arises due to actions at four receptor types:
    1. Sodium channel inhibition → prolonged QRS
    2. ɑ1-adrenoreceptor antagonism → hypotension
    3. Muscarinic AChR → anticholinergic toxidrome
    4. H1 & H2 histamine receptor antagonism → histamine-related sedation

  • The predominant cause of death is cardiac depression by sodium channel blockade with resultant decrease in cardiac output

Cardiovascular

  • Cardiovascular collapse is mostly due to a sodium channel stabilising effect
  • There is blockade of fast sodium channels in the myocardial conduction system
  • This leads to increased QRS duration initially, progressing to:
    • Decreased myocardial excitability
    • Bradycardia and asystole

  • Typical ECG features:
    • Prolonged PR interval
    • Broad QRS complex - prolonged QRS is a predictor of ventricular arrhythmias and seizures, especially once >160ms
    • Prolongation of the QT intervals
    • Non-specific ST segment and T wave changes
    • Atrioventricular block or RBBB
    • Brugada electrocardiographic pattern

  • There is also a dose-dependent decrease in myocardial contractility due to noradrenaline and serotonin re-uptake inhibition
  • ɑ1-adrenergic receptor blockade causes profound vasodilation
  • There is thus distributive shock

Neurological

  • Central anti-histaminergic and anti-cholinergic activity occurs
  • Correlates with QRS >100ms
  • This leads to the anti-cholinergic toxidrome of 'hot, mad, blind, red, dry'

  • Noradrenaline and serotonin re-uptake inhibition also reduces the seizure threshold

Risk assessment

  • Based on dose:
    • <5mg/kg: minimal symptoms
    • 5 - 10mg/kg
      • drowsiness and mild anticholinergic features
    • >10mg/kg: potentially life threatening toxicity
      • Potential for coma, hypotension, seizures, cardiac dysrhythmias
      • Anticholinergic affects are often masked by the coma
    • >30mg/kg: severe toxicity
      • pH-dependent cardiotoxicity and coma expected to last >24 hours
      • Usually manifests within 2 hours

  • By QRS:
    • >100ms is predictive of seizures
    • >160ms is predictive of ventricular tachycardia

Resuscitation

  • The mainstay of treatment for severe toxicity involves aggressive supportive care
  • The goals of treatment are:
    • Na+ ∽155mmol/L
    • pH 7.50 - 7.55
  1. Prompt intubation for patients with depressed consciousness
    • Attempt pre-intubation ECG to recognise signs of toxicity early and avoid delays in treatment
    • Consider activated charcoal after airway secure if within 1hr of overdose and ingested dose is >10mg/kg

  2. Hyperventilation with goal pH 7.50 - 7.55 (old school)

  3. Management of various cardiovascular sequelae:
    • Hypotension and distributive shock
      • 20ml/kg crystalloid bolus with target MAP >65mmHg
      • Noradrenaline infusion or adrenaline infusion
      • Sodium bicarbonate 2 mmol/kg (2ml/kg 8.4%)

    • Ventricular arrhythmias
      • Sodium bicarbonate 2 mmol/kg IV repeated every 1-2 minutes to restore a perfusing rhythm
        • 100ml 8.4% NaHCO3 contains 100mmol each of Na+ and HCO3- i.e. give 2ml/kg of 8.4% NaHCO3
        • Once reaching 6mmol/kg seek specialist toxicologist advice

      • It is unlikely that defibrillation will work, so other drugs include:
        • A prolonged QTc should also prompt administration of magnesium
        • Lidocaine 1 - 1.5 mg/kg IV is third line when the pH is >7.50
        • Intralipid only according to expert advice, dosing as per LA toxicity
      • NB class 1a & 1c antidysrhythmic agents (e.g. procainamide), isoprenaline, amiodarone, digoxin and β-blockers are contraindicated

    • Cardiac monitoring for all patients for 6hrs following overdose regardless of dose ingested

  4. Mainly need to manage seizures
    • Check blood glucose and sodium as standard practice
    • Benzodiazepines are the mainstay e.g. IV lorazepam 4mg | midazolam 10mg | diazepam 10mg
    • Sodium bicarbonate will help alkalinise serum and prevent further TCA crossing the BBB
    • May need RSI to terminate the seizure; high risk of cardiac arrest peri-intubation

  5. Catheterise as may be in urinary retention
    • No role for forced diuresis
    • Passive management of hyperthermia

Sodium bicarbonate

  • Provides a trifecta of benefits:
    1. Provides a source of sodium:
      • Substrate for cardiac sodium channels to function
      • Displaces TCAs from cardiac sodium channels

    2. Alkalinises serum
      • Increases protein binding of TCAs
      • Offsets metabolic acidosis to improve haemodynamics

    3. Provides volume expansion