Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

suspected or confirmed TCA overdose

1st line – supportive care and monitoring

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ACUTE
|
suspected or confirmed TCA overdose
1st line – 

supportive care and monitoring

The patient should be rapidly stabilised. Assess airway, breathing, and circulation; obtain intravenous access; attach a cardiac monitor; and obtain an ECG to look for QRS prolongation.[Figure caption and citation for the preceding image starts]: Classic ECG changesFrom the collection of R.S. Hoffman; used with permission [Citation ends].com.bmj.content.model.Caption@71c55eb6

Acidosis, hypoxia, and electrolyte abnormalities should be corrected initially.

Plus – gastrointestinal decontamination

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ACUTE
|
suspected or confirmed TCA overdose
|
with ingestion within 2 hours
Plus – 

gastrointestinal decontamination

Treatment recommended for ALL patients in selected patient group

The aim is to bind any free drug in the gastrointestinal tract with activated charcoal before absorption occurs.[28]

Attention to the airway is critical to avoid aspiration. Pulmonary aspiration of activated charcoal may be life-threatening.

Primary options

activated charcoal: 1 g/kg orally as a single dose, repeat every 2-4 hours if required

Plus – sodium bicarbonate

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ACUTE
|
suspected or confirmed TCA overdose
|
with QRS >100 milliseconds or pH <7.45
Plus – 

sodium bicarbonate

Treatment recommended for ALL patients in selected patient group

Sodium bicarbonate boluses should be given to narrow the QRS to <100 milliseconds, aiming for a maximum pH of between 7.5 and 7.55. There is some debate as to whether these initial boluses should be followed by a continuous infusion or additional boluses as needed; whichever is used, it is important to keep serum sodium <155 mEq/L and serum pH <7.55.[31]​ 

Two approaches that may be necessary to avoid excessive alkalemia include giving 3% sodium chloride without bicarbonate, or allowing for a small degree of permissive hypercapnia on the ventilator to allow for further bicarbonate boluses.

Primary options

sodium bicarbonate: consult specialist for guidance on dose

Plus – sodium bicarbonate plus anti-arrhythmic therapy

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ACUTE
|
suspected or confirmed TCA overdose
|
with arrhythmias
Plus – 

sodium bicarbonate plus anti-arrhythmic therapy

Treatment recommended for ALL patients in selected patient group

Major arrhythmias usually occur in association with other ECG changes or in the presence of complications such as coma, hypotension, or seizures. However, they may also occur in patients with only minor ECG abnormalities. Acidosis, hypoxia, and electrolyte abnormalities should be corrected initially.

Sodium bicarbonate may be effective at treating both tachyarrhythmias and bradyarrhythmias, even in the absence of metabolic acidosis.[21] The incidence of ventricular arrhythmias requiring therapy other than sodium bicarbonate is very low. Anti-arrhythmic drugs should generally be avoided since they may lead to an exacerbation.

Sodium bicarbonate boluses should be given, aiming for a maximum pH of between 7.5 and 7.55. There is some debate as to whether these initial boluses should be followed by a continuous infusion or additional boluses as needed; whichever is used, it is important to keep serum sodium <155 mEq/L and serum pH <7.55.[31]​ Aim to maintain QRS duration <100 milliseconds.

Consider use of magnesium sulfate for tachyarrhythmias that persist despite correction of acidosis and administration of sodium bicarbonate. Magnesium infusion or atrial overdrive pacing may also be of benefit in torsades de pointes. There is some limited clinical evidence of the benefit of lidocaine.[31][39]​​​​

For significant bradyarrhythmias (such as Mobitz Type II or complete heart block) that are unresponsive to treatment with sodium bicarbonate, consider use of isoprenaline as a temporary measure until temporary pacing is established. For severe life-threatening arrhythmias that are resistant to sodium bicarbonate, consider the use of intravenous lipid emulsion.[40][41][42]

Primary options

sodium bicarbonate: consult specialist for guidance on dose

Secondary options

magnesium sulfate: consult specialist for guidance on dose

OR

lidocaine: consult specialist for guidance on dose

OR

isoprenaline: consult specialist for guidance on dose

Plus – intravenous fluids plus sodium bicarbonate

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ACUTE
|
suspected or confirmed TCA overdose
|
with hypotension
Plus – 

intravenous fluids plus sodium bicarbonate

Treatment recommended for ALL patients in selected patient group

TCA poisoning can cause severe refractory hypotension as a result of impaired myocardial contractility, reduced cardiac output, and decreased peripheral vascular resistance. Sodium bicarbonate should be given to reduce cardiotoxicity.

Hypotension should be treated with intravenous crystalloid/colloid initially.

Sodium bicarbonate rapid intravenous boluses may correct acidosis and improve myocardial contractility. The risk of this therapy is making the patient too alkalotic. Patients on intravenous sodium bicarbonate need regular monitoring of pH and electrolytes. Serum pH should not exceed 7.5 to 7.55 and serum sodium should be <155 mEq/L. QRS duration should also be aimed to be kept <100 milliseconds.

Central venous pressure monitoring is likely to be required in patients whose blood pressure is unresponsive to intravenous fluids and sodium bicarbonate.

Primary options

sodium bicarbonate: consult specialist for guidance on dose

Consider – vasopressor or glucagon or extracorporeal membrane oxygenation

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ACUTE
|
suspected or confirmed TCA overdose
|
with hypotension
Consider – 

vasopressor or glucagon or extracorporeal membrane oxygenation

Additional treatment recommended for SOME patients in selected patient group

Vasopressors, such as noradrenaline (norepinephrine) or phenylephrine, should only be commenced in discussion with a medical toxicologist and intensive care physician.

High-dose glucagon or terlipressin can be considered, although clinical evidence is limited.[31][33][34][35][36]​​​​

Extracorporeal membrane oxygenation can be considered for severe cases of refractory hypotension.[29][30][31]​​

Primary options

noradrenaline (norepinephrine): consult specialist for guidance on dose

OR

phenylephrine injection: consult specialist for guidance on dose

Secondary options

glucagon: consult specialist for guidance on dose

OR

terlipressin: consult specialist for guidance on dose

Plus – hyperventilation plus sodium bicarbonate

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ACUTE
|
suspected or confirmed TCA overdose
|
with cardiac arrest
Plus – 

hyperventilation plus sodium bicarbonate

Treatment recommended for ALL patients in selected patient group

Cardiac arrest caused by TCAs should be treated by systemic alkalinisation with sodium bicarbonate and hyperventilation.

Standard cardiac resuscitation efforts should be implemented. Attempts at resuscitation should continue for at least 1 hour.

Primary options

sodium bicarbonate: consult specialist for guidance on dose

Plus – sodium bicarbonate plus benzodiazepine or barbiturate or propofol

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ACUTE
|
suspected or confirmed TCA overdose
|
with seizures
Plus – 

sodium bicarbonate plus benzodiazepine or barbiturate or propofol

Treatment recommended for ALL patients in selected patient group

Although most seizures are brief and self-terminating, they can cause worsening of acidosis and cardiotoxicity. Acidosis, hypoxia, and electrolyte abnormalities should be corrected initially. Rapid intravenous bolus of hypertonic sodium bicarbonate should be given as long as serum pH does not exceed 7.5 to 7.55. There is some debate as to whether these initial boluses should be followed by a continuous infusion or additional boluses as needed; whichever is used, it is important to keep serum sodium <155 mEq/L and serum pH <7.55.[31]​ Aim to maintain QRS duration <100 milliseconds.[25]

Persistent seizures should be treated with a benzodiazepine, such as diazepam or lorazepam. Administration of benzodiazepines may cause further impairment of consciousness level and respiratory depression.

Consider the use of barbiturates or propofol if seizures are not controlled with benzodiazepines.

Phenytoin is contraindicated as it does not improve seizures and may worsen cardiac toxicity.[43]

Primary options

sodium bicarbonate: consult specialist for guidance on dose

Secondary options

diazepam: consult specialist for guidance on dose

OR

lorazepam: consult specialist for guidance on dose

Tertiary options

phenobarbital: consult specialist for guidance on dose

OR

propofol: consult specialist for guidance on dose

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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