TCA toxicity

Peer Reviewed Dr Emily Austin – Toxicologist Toronto.

This is your one stop page for TCA overdose. Find out how to manage the acute overdose and the potential complications. We have also covered the basic TCA pharmacology and a tutorial about sodium channel blockade and the ECG, find out why the QRS will widen. Finally, test your knowledge afterwards with ECGs and Tox conundrums which have greater detail on managing the TCA overdose.

Common TCAs include: Amitriptyline, Clomipramine, Dothiepin (more likely to cause seizures than the others), Doxepin, Imipramine, Nortriptyline and Trimipramine.

AUDIO TCA Overdose talks + what to do when bicarbonate doesn’t work
Pharmacology of TCAs BSCC video
TCAs and the ECG video
Key TCA knowledge:
  • >10mg/kg is potentially life threatening
  • <5mg/kg = Minimal symptoms
  • 5-10mg/kg = Drowsiness and mild anticholinergic features
  • >10mg/kg = Potential for coma, hypotension, seizures, cardiac dysrhythmias. Anticholinergic affects are often masked by the coma
  • >30mg/kg = severe toxicity with pH-dependent cardiotoxicity and coma expected to last >24 hours.
  • Severe toxicity usually manifests within 2 hours but any overdose requires close cardiac monitoring for 6 hours post ingestion.
  • QRS widens due to fast sodium channel blockade, >100ms is predictive of seizures and >160ms is predictive of ventricular tachycardia
  • The mainstay of treatment for severe toxicity involves aggressive supportive care including the use of sodium bicarbonate for dysrhythmias and widening of the QRS alongside hyperventilation to maintain a pH >7.5-7.55

How to manage the toxic overdose i.e. >10mg/kg with signs of toxicity:

  • Reduced GCS (<12) prompt intubation and hyperventilation is indicated (maintain pH >7.5-7.55)
  • Pre-intubation and on arrival it is vital to get an ECG looking for signs of toxicity (widening of the QRS, large terminal R wave in aVR increased R/S ratio (>0.7) in aVR and QT prolongation). If present give sodium bicarbonate 1-2mmol/kg until the effect is seen because even during the quickest of intubations you will cause a state of acidosis which will exacerbate TCA toxicity.
  • Ventricular dysrhythmias: Cardioversion is unlikely to be successful, give repeated doses of sodium bicarbonate (2 mmol/kg) every 1-2 minutes to a maximum of 6mmol/kg or until a perfusing rhythm is restored. Lignocaine 1.5mg/kg IV is third line when a pH of >7.5 is established. If your patient is not responding to the doses and drugs above urgently call a toxicologist.
  • Hypotension is treated with IV crystalloid, sodium bicarbonate (to a maximum of 6mmol/kg), adrenaline or noradrenaline.
  • Seizures are managed with benzodiazepines
  • Antidote: Sodium bicarbonate (and hyperventilation). Sodium bicarbonate should be given as a bolus and not an infusion. Once the patient is hyperventilated to a pH >7.5 sodium bicarbonate should not be required. See below for more details on the correct administration of sodium bicarbonate as too much can cause iatrogenic death.
  • Charcoal can be given once the airway is secure and via an NG tube. Never give in a patient without a secure airway due to the rapid decline in GCS and the risk of seizures
  • Usually the patient’s ventilation can be altered 12-24 hours post ingestion to a pH of 7.35-7.4 with close monitoring of the ECG and haemodynamics, if there are any ECG changes or haemodynamic compromise then the patient is still toxic and requires further hyperventilation

How to correctly give sodium bicarbonate and what to do if is is not working:

  • Sodium bicarbonate is a wonderful antidote for classic TCA overdoses but too much can be fatal and not all sodium channel blocking drugs respond the same.
  • Bear in mind the 3 end goals of sodium loading and perform 30-minute repeat arterial blood gases to ensure you are not over target:
    1. Narrowing the QRS to normal for the patient or less than 140ms (toxicologists have varied opinions but between 120-140ms is safer than too much sodium bicarbonate)
    2. Maximum Sodium of 155 mmol/L
    3. pH aim of 7.5 to 7.55
  • EXCESS Sodium Bicarbonate can kill. You risk severe alkalaemia, hypernatraemia and hypokalemia. Don’t go over a maximum of 6mmol/kg without discussion with a clinical toxicologist.
  • Intubate and hyperventilate to a pH of 7.5 to 7.55
  • 3% saline can be given to achieve a sodium of 155 mmol/L if further bicarbonate can not be given.
  • Lidocaine 1-1.5mg/kg slow IV push, followed by 20-50 ug/kg/min infusion
  • Intralipid

RRSIDEAD approach


  • CNS depression (even GCS 12) requires prompt intubation and hyperventilation (aiming for pH 7.5-7.55)
    • Pre-intubation and on arrival it is vital to get an ECG looking for signs of toxicity (widening of the QRS, large terminal R wave in aVR increased R/S ratio (>0.7) in aVR and QT prolongation). If present give sodium bicarbonate 1-2mmol/kg until effect is seen because even during the quickest of intubations you will cause a state of acidosis which will exacerbate TCA toxicity.
  • Ventricular dysrhythmias:
    • Sodium bicarbonate 2 mmol/kg IV repeated every 1-2 minutes to restore a perfusing rhythm, multiple doses maybe required.
    • It is unlikely that defibrillation will work.
    • Lignocaine 1-1.5 mg/kg IV is third line when the pH is >7.5.
    • If requiring the kitchen sink approach some people have used intralipid but this is not standard therapy and expert advice should be sought.
    • Type Ia antidysrhythmic agents (e.g. procainamide), amiodarone and beta-blockers are contraindicated
  • Hypotension:
    • 20ml/kg crystalloid bolus, sodium bicarbonate 2 mmol/kg may restore a MAP >65.
    • Failing this adrenaline and noradrenaline infusions can be used (peripherally at first until able to insert a central line when higher doses can be used, of note the risks of extravasation i.e. tissue necrosis is the same as for push dose pressures and using meteraminol/aramine. Make sure you have a big flowing peripheral line).
    • Noradrenaline dose: 0.15mg/kg in 50ml D5W at 1-10ml/hr (0.05 – 0.5 mcg/kg/min).
    • Adrenaline dose: 0.15mg/kg in 50ml D5W at 1-10ml/hr (0.05 – 0.5 mcg/kg/min).
  • Seizures:
    • Check the patient is not in a dysrhythmia
    • Can be managed with benzodiazepines (varying doses in the textbooks, easy method is 0.1mg/kg IV for lorazepam (max 4mg) / midazolam (max 10mg) / diazepam (max 10mg). Or…
    • Lorazepam 0.1mg/kg max 4mg
    • Diazepam 0.15mg/kg max 10mg
    • Midazolam 0.2mg/kg max 10mg
    • With TCAs it is likely that sodium bicarbonate maybe required if the patient is seizing to help alkalinise the serum and prevent further TCA crossing the blood brain barrier.
    • If the above measures do not work there will be an escalating spiral of acidosis and further TCA binding to the CNS and myocardium resulting in coma, haemodynamic instability and death. Neuromuscular blockade with an RSI maybe the only way to terminate the seizure. This will require a highly skilled operator and expert advice due to the risks of cardiac arrest peri-intubation.

Risk Assessment

  • Ingestion of >10mg/kg is potentially lethal
  • Toxicity usually manifests within 2 hours but any reported ingestion overdose requires at least 6 hours of observation
  • <5mg/kg = Minimal symptoms
  • 5-10mg/kg = Drowsiness and mild anticholinergic symptoms
  • >10mg/kg = Hypotension (secondary to alpha-blocking effects and impaired contractility), seizures, cardiac dysrhythmias and coma, rapid progression may mean than anticholinergic phase is not seen.
  • >30mg/kg Severe toxicity, with prolonged come >24 hours and cardiac instability.

Supportive Care

  • If anticholinergic, monitor bladder volumes (may go into retention)
  • Small doses of benzodiazepines maybe required for agitation
  • Intubated patients need to be hyperventilated to pH 7.5-7.55
  • See FASTHUGSINBED for further supportive care.


  • Screening: 12 lead ECG, BSL, Paracetamol level
  • Specific: Some centres can get TCA levels but these maybe delayed and you need to be able to diagnose TCA overdose clinically and on the ECG. See Ed Burns ECG page on TCAs.
  • ECG features of sodium channel blockade include:
    • Prolonged QRS interval (>100ms is predictive of seizures, >160ms is predictive of ventricular tachycardia)
    • Large terminal R wave in aVR
    • Increased R/S ratio (>0.7) in aVR
    • QT prolongation is noted secondary to potassium channel blockade but also due to the widening of the QRS.


  • Activated charcoal is not recommended for ingestions <10mg/kg as there is a good outcome with supportive care.
  • >10mg/kg activated charcoal is advised but only after the airway is secured by endotracheal intubation
  • Activated charcoal should never take priority over resuscitation

Enhanced Elimination

  • Not clinically useful



  • Patients who have a normal 12 lead ECG (or no change from their baseline), normal mental status, no cardiovascular instability or seizures at 6 hours do not require any further monitoring and are medically fit for discharge or psychiatric evaluation
  • Patients with minor abnormalities need a prolonged period of careful observation including cardiac until symptoms have resolved.
  • Patients requiring inotropic support or intubation require intensive care
Additional TCA Resources
toxicology library antidote 700 1

Toxicology Library


Dr Neil Long BMBS FACEM FRCEM FRCPC. Emergency Physician at Kelowna hospital, British Columbia. Loves the misery of alpine climbing and working in austere environments (namely tertiary trauma centres). Supporter of FOAMed, lifelong education and trying to find that elusive peak performance.

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