Poisoning - Tricyclic antidepressant

Disclaimer These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.  Read the full CAHS clinical disclaimer

Aim 

To guide PCH ED staff with the assessment and management of tricyclic antidepressant poisoning in children.

This guideline is a general approach to tricyclic antidepressant poisoning. For specific details please contact Poisons Information: 131126 or refer to the Toxicology and Toxinology – Therapeutic Guidelines.

Background

Agents

• Amitriptyline
• Clomipramine
• Dosulepin (Dothiepin)
• Doxepin
• Imipramine
• Nortriptyline
• Trimipramine

Tricyclic antidepressants (TCAs) act on a variety of receptors whose actions include:

• Noradrenaline reuptake inhibition
• Central and peripheral anticholinergic effect
• Fast sodium channel blockade in the myocardium
• Peripheral alpha1-adrenergic receptor blockade

The life threatening effects of acute tricyclic antidepressant (TCA) overdose are:

• Rapid onset of coma
• Seizures
• Cardiac dysrhythmias.

Hypotension and central and peripheral anticholinergic effects may also be seen.

Risk Assessment

• Patients who ingest a large dose of TCA usually develop evidence of intoxication within 2-4 hours, and always within 6 hours.
• Any suspected ingestion > 5mg/kg should be admitted for 6 hours of monitoring in hospital.
• If there is suspicion of deliberate self-poisoning, patients are to be referred for evaluation in hospital, regardless of the dose ingested.

Typical clinical course

Common effects following acute TCA ingestion include:

• Drowsiness
• Ataxia
• Sinus tachycardia
• Dilated pupils
• Decreased bowel sounds
• Ileus and urinary retention 

Life threatening effects following acute TCA overdose are:

• Coma
• Seizures
• Ventricular dysrhythmia
• Hypotension
• Central and Peripheral anticholinergic effects may also be seen.

Ingested dose	Symptoms and Disposition
< 5 mg/kg	Minimal toxicity Patients do not require decontamination or referral to hospital except in cases of deliberate overdose
5 - 10mg/kg	Major symptoms unlikely Mild anticholinergic effects may be present Drowsiness Tachycardia Patients should be referred to hospital for evaluation and observation and may be discharged if asymptomatic at 6 hours post ingestion.
> 10mg/kg	Life threatening effects: Coma Seizures Cardiac dysryhythmias Hypotension Anticholinergic effects are likely but often masked by coma Patients are to be admitted to the Paediatric Critical Care (PCC). Intubation and hyperventilation may be required.
> 30mg/kg	Severe toxicity with pH-dependent cardiotoxicity and coma expected to at least >24 hours Patients are to be admitted to PCC. Intubation and hyperventilation may be required.

Investigations

Screening (for deliberate overdose)

• Blood Glucose Level (BGL)
• Paracetamol level (if deliberate ingestion). 

Specific

• Serial 12 lead ECG
• SInus tachycardia
  
  • Prolonged QRS interval (sodium channel blockade)
    • > 100ms predicts risk of seizures
    • > 160ms predicts risk of ventricular tachycardia
  • Large terminal R wave in aVR
  • Increased R/S ratio (> 0.7) in aVR
  • Prolonged QT interval (potassium channel blockade)
• Blood gas (pH)
• Serum electrolytes (large doses of sodium bicarbonate can cause hypokalaemia)

Management

Resuscitation

Overdose may be life-threatening and should be managed in a resuscitation bay with cardiac monitoring. Cardiac monitoring should continue for at least 6 hours post-ingestion or until resolution of toxicity.

Reduced level of consciousness

• Intubation and hyperventilation are indicated if the GCS falls below 12.
• Sodium bicarbonate boluses should be given prior to intubation to optimise cardiovascular status (see antidote section below).
• The patient should receive positive pressure ventilation during the apnoeic phase to prevent respiratory acidosis.
• Once intubated, hyperventilate to a pH of 7.50 to 7.55.

Ventricular dysrhythmias 

• Sodium bicarbonate boluses should be given until restoration of a perfusing rhythm and narrowing of the QRS (see antidote section below). 
• Cardioversion and defibrillation are unlikely to be effective.
• Type Ia antidysrhythmic agents (e.g. procainamide), amiodarone and beta-blockers are contraindicated.
• Serial ECGs should be performed every 5-10 minutes until ECG abnormalities are stabilised.

Hypotension

• Treat with IV crystalloid solutions (10-20 mL/kg) and assess response.
• Refractory hypotension may require sodium bicarbonate and adrenaline (epinephrine) or noradrenaline (norepinephrine) infusion.

Seizures

• Benzodiazepines are first-line treatment.
• Phenytoin is contraindicated.
• Refer to Seizure – Medication for further guidance.

Cardiac Arrest

• Do not cease resuscitation efforts until the patient has been intubated, treated with hyperventilation and sodium bicarbonate to achieve a pH of 7.50 to 7.55, and discussed with a Clinical Toxicologist.

Decontamination

Activated charcoal:

• 1 month to 18 years: 1gram/kg (up to a maximum 50 grams) as a single dose, indicated for ingestions > 10mg/kg but should not be given until the airway is secured by ETT and after dealing with resuscitation requirements.

Enhanced Elimination

No role.

Antidote²

Sodium bicarbonate 8.4%:

• 1 to 2mL/kg up to 100mL (1 to 2 mmol/kg up to 100mmol) IV bolus every 3 to 5 minutes, titrated to narrowing of the QRS complex and aiming for a pH of 7.50 to 7.55. 
• Maximum dose 6mL/kg (6mmol/kg). Seek urgent clinical toxicology advice if not responding to maximum dose.
• Monitor serum potassium levels if giving large doses of sodium bicarbonate.

Disposition

• Any patient who is asymptomatic at 6 hours with a normal ECG can be medically cleared.
• Ingestions > 5mg/kg should be observed in hospital for 6 hours.
• Patients who have mild ECG or mental state changes should be admitted to a medical ward for careful observation, cardiac monitoring, and regular ECGs.
• Patients with significant TCA overdose will require PCC admission. 

Nursing

• Baseline observations: heart rate, respiratory rate, oxygen saturation blood pressure and neurological observations
• Minimum of hourly observations should be recorded whilst in the Emergency Department
• Any significant changes should be reported immediately to the medical team
• Baseline ECG on arrival and as required throughout presentation
• Continual cardiac monitoring
• Blood glucose level for patients with a reduced level of consciousness
• Ensure the patient is always aided when ambulating to prevent a fall
• Fluid balance
• Bladder scan (urinary retention is a common anticholinergic effect).

References

1. Toxicology and Toxinology – Therapeutic Guidelines
2. Handbook AM. AMH Children's Dosing Companion Australia: AMH; 2020 [Available from: https://childrens.amh.net.au/.

Endorsed by:	Director, Emergency Department	Date:	Nov 2020
		Review date:	Nov 2023

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