Tricyclic Antidepressant Toxicity CCC


Tricyclic Antidepressants (TCA) are weak bases (pKa 8.5) that can cause life-threatening sodium channel toxicity leading to:

  1. anticholinergic effects
  2. inhibition of catecholamine reuptake (initial increase in sympathetic tone -> prolonged decrease)
  3. profound alpha-adrenergic blockade
  4. sodium channel blockade -> cardiotoxicity and CNS effects


  • having taken a large quantity of TCA (patients may be asymptomatic for 2-3 hours post ingestion)
  • will develop signs of major toxicity within 6 hours
    – > 10mg/kg potentially life threatening
    – > 30mg/kg will develop pH dependent toxicity + coma for more than 24 hours


  • CVS – dry mucous membranes, tachycardia, hypertension -> hypotension -> cardiovascular collapse (arrhythmia), postural hypotension, dehydration
  • CNS – nystagmus, dizziness, agitation, decreases level of consciousness, unconscious/coma, seizures, increase in tone, clonus, tremor, hypereflexia, pupillary dilation, blurred vision
  • GI – N+V, abdominal pain, dry mouth, ileus
  • METABOLIC – severe metabolic acidosis, fever
  • GU – urinary retention
  • SKIN – flushed
  • anticholinergic: “blind as a bat, red as a beet, hot as a hare, dry as a bone, mad as a hatter”


  • ABG – metabolic acidosis
  • ECG:
    -> sinus tachycardia
    -> PR prolongation
    -> RAD
    -> R wave > 3mm in aVR
    -> prolonged QT interval (>430ms)
    -> QRS prolongation (>100ms)
    -> VF/VT/asystole
    -> 2nd or 3rd HB
    -> RBBB
  • Bloods – renal impairment



  • supportive care of airway, breathing and circulation
  • a number of anti-arrhythmics are contra-indicated as they prolong depolarisation -> use lignocaine, phenytoin, Mg2+, hypertonic saline.
  • often need PAC
  • volume resuscitation
  • treat seizures with benziodiazepines (ist line), barbiturates (2nd line), other options include: propofol

Electrolyte and Acid-base Abnormalities

  • IV NaHCO3 + hyperventilation to ensure pH is >7.5

How NaHCO3 works:

  • TCA are weak bases
  • increasing the serum pH with bicarbonate -> increases the proportion of non-ionised drug which -> increase in drug distribution throughout rest of body and away from heart
  • increased Na+ also overcomes the Na+ receptor blockade
  • alkalinsation also accelerates the recovery of Na+ channels by neutralising the protonation of the drug receptor complex

Specific Treatment

  • see above

Underlying Cause

  • prevent absorption: gastric lavage and charcoal if presents within 1 hour,
  • enhanced elimination: haemodialysis not recommended in TCA OD c/o small amount of free drug in plasma

References and Links

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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