Digoxin toxicity

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

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

acute, acute on chronic, or chronic toxicity

1st line – supportive care

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1st line –

supportive care

Perform an Airway, Breathing, Circulation, Disability, Exposure (ABCDE) assessment and re-assess the patient regularly throughout treatment.[26]

Be alert to the possibility of cardiac arrest.[1]
- Resuscitation and supportive treatment may be needed.
- If so, continue resuscitation for at least 1 hour. Only stop after discussion with a senior clinician.[1]
Observe for electrolyte abnormalities and correct if found to be present (see groups below).[1]
Collect a sample to measure digoxin concentration, if possible.[1]
Use digoxin-binding therapy (see Digoxin-binding therapy below).

Ensure rapid fluid resuscitation in patients with hypovolaemia.[1]

If the patient has signs of haemodynamic insufficiency and/or compromise (e.g., hypotension, altered consciousness), give digoxin-specific antibody (Fab) fragments as primary management (see Digoxin-binding therapy below).

Refer patients with fluid-resistant hypotension to critical care and involve paediatrics for children.[1]

Discuss symptomatic patients and any patients with ECG abnormalities with critical care.[1]

Consult your approved clinical toxicology resource (e.g., TOXBASE in the UK) and/or seek advice from your national or regional poisons information service.[1][22] National Poisons Information Service: TOXBASE Opens in new window

Discontinue the digoxin and any other rate control agents that potentiate the effects of digoxin.[20]

Check and monitor:[1]

Cardiac rhythm
Vital signs
Capillary blood glucose
Pupil size
Blood pressure
- Hypotension may occur.

Consider any indications that poisoning may have been intentional as an act of self-harm:[22]

Take urgent steps to establish the patient’s emotional and mental state at the same time as assessing physical risk.
Request a psychosocial assessment by a trained member of staff. Do not delay this until after medical treatment unless life-saving treatment is needed.
Offer a safe, supportive environment for the patient to wait for treatment, with regular supervision and contact from a named staff member to ensure safety.
See Suicide risk mitigation.

Observe all patients who have required assessment for at least 6 hours after ingestion. After this time, consider discharging patients if their digoxin concentration has returned to normal and they have a normal ECG. Instruct them to return if symptoms develop.[1]

If a mixed overdose has occurred, consult your approved clinical toxicology resource (e.g., TOXBASE in the UK). There may be specific management recommendations to bear in mind, particularly regarding the amount of time the patient should be monitored for.[1]

Plus – observation for hyperkalaemia ± correction

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Plus –

observation for hyperkalaemia ± correction

Treatment recommended for ALL patients in selected patient group

Correct electrolyte abnormalities in line with your local protocols. The following recommendations are from the National Poisons Information Service in the UK.[1] National Poisons Information Service: TOXBASE Opens in new window

Adults

Give adults with severe hyperkalaemia:[1]

10% calcium chloride by slow intravenous injection with continuous cardiac monitoring, or 10% calcium gluconate by slow intravenous injection with continuous cardiac monitoring
- Repeat the initial dose after 5-10 minutes if there is no improvement in the ECG, up to a maximum dose of 30 mL (6.8 mmol).
Nebulised salbutamol
10 units of short acting insulin with 100 mL of 20% dextrose intravenously over 5 minutes.
- Repeat if the hyperkalaemia does not improve.

Consider: [1]

Correcting metabolic acidosis with intravenous sodium bicarbonate.
Haemodialysis in patients with renal failure to treat severe hyperkalaemia or acidosis.
- Always monitor potassium repeatedly if digoxin-specific antibody (Fab) fragments are administered as the patient’s potassium concentration may fall rapidly.[1]

Significant hyperkalaemia is associated with a poor prognosis if not treated.[27]

Consult your local protocols.

Children (under 12 years)

Always discuss children with hyperkalaemia rapidly with your paediatric department and refer for specialist management.[1]

Plus – observation for hypokalaemia ± correction

Plus – observation for hypomagnesaemia ± correction

Consider – digoxin-binding therapy

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Consider –

digoxin-binding therapy

Additional treatment recommended for SOME patients in selected patient group

For any patient with arrhythmias, consult a senior specialist colleague (cardiology or toxicology, as necessary) and refer to your approved clinical toxicology resource (e.g., TOXBASE in the UK). National Poisons Information Service: TOXBASE Opens in new window

Urgently administer digoxin-specific antibody (Fab) fragments (also known as digoxin immune Fab) in patients with strongly suspected or known digoxin toxicity plus:[1][27]

Cardiac arrest
Life-threatening ventricular arrhythmia or severe bradyarrhythmia
Severe hyperkalaemia (potassium concentrations >6.5 mmol/L [>6.5 mEq/L]) resistant to conventional treatment.

Repeated doses may be required, for example if the patient remains unstable with arrhythmias or hyperkalaemia.[1]

Digoxin-specific antibody (Fab) fragments tend to be used in two doses:[1]

Full neutralisation: calculated to neutralise all the digoxin load
Half neutralisation: calculated to neutralise half of the digoxin load.

The ‘half neutralisation’ dose is adequate for most patients. It is calculated using the patient's weight and the serum digoxin concentration.

Consult your approved clinical toxicology resource (e.g., TOXBASE in the UK) to assist with calculation of the appropriate dose. In the situation of cardiac arrest when time is critical and these variables may not be known, your approved clinical toxicology resource provides advice on empirical dosing.[1] National Poisons Information Service: TOXBASE Opens in new window

Frequently monitor the patient’s serum potassium and magnesium. Correct hypomagnesaemia and hypokalaemia, if present, before or during administration of digoxin-specific antibody (Fab) fragments (see observation for hyperkalaemia ± correction, observation for hypokalaemia ± correction, and observation for hypomagnesaemia ± correction, above).[27]

The antibody fragments will further lower potassium.[27]
Patients who receive digoxin-specific antibody (Fab) fragments have a drop in the serum potassium as it moves intracellularly.[28][29][30]
Some patients who have been treated for hyperkalaemia and who have also received digoxin-specific antibody (Fab) fragments develop profound hypokalaemia.
Therefore, serial potassium measurements are made when patients receive both digoxin-specific antibody (Fab) fragments and other therapies to decrease potassium.[31]

The therapeutic effect of digoxin-specific antibody (Fab) fragments is usually seen within 15-30 minutes of administration.[1] Look for an improvement in the patient’s haemodynamic status, with pulse and blood pressure returning to normal. The potassium will also reduce.

Monitor the patient until there is clear clinical improvement; in practice, monitoring will continue for at least 24-48 hours. Bear in mind that after an initial response to digoxin-specific antibody (Fab) fragments, toxicity can develop again. Known as ‘rebound toxicity’, this can occur 12-24 hours after treatment, but reportedly even up to 10 days after treatment in patients with renal failure.[27]

Practical tip

Measure serum digoxin concentration every 24 hours until the patient is well and then re-establish the patient onto the therapeutic dose of digoxin, if appropriate. Re-check after a further 3 days.

Bear in mind that elevated digoxin concentrations can occur after treatment with digoxin-specific antibodies.[25] Routinely used assays measure both free digoxin and Fab-digoxin complexes and therefore report apparently high digoxin levels following treatment with digoxin-specific antibodies.[1]

Primary options

digoxin immune Fab: children and adults: consult specialist for guidance on dose

Consider – atropine or temporary pacing wire

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Consider –

atropine or temporary pacing wire

Additional treatment recommended for SOME patients in selected patient group

If digoxin-binding therapy is not immediately available, use atropine in patients with symptomatic bradycardia or atrioventricular (AV) block.[1][27][31][32] Repeat doses may be required. Paediatric patients with symptomatic bradycardia require lower doses of atropine.

Alternatively, consider inserting a temporary pacing wire in patients with evidence of significant bradycardia or AV block and haemodynamic compromise if digoxin-specific antibody (Fab) fragments are not readily available.[1]

Consider using digoxin-specific antibody (Fab) fragments if they have become available after the patient has been treated with atropine.[1]

Primary options

atropine: children and adults: consult specialist for guidance on dose

Consider – activated charcoal

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Consider –

activated charcoal

Additional treatment recommended for SOME patients in selected patient group

Consider activated charcoal if the patient is symptomatic, or has ingested 20 micrograms/kg or more digoxin, or ingested any amount of a toxic plant.[1] Only do this provided the patient’s airway can be protected and gut motility is normal.[1]

The activated charcoal will reduce absorption.[1]

Ideally, give the activated charcoal within 2 hours of acute ingestion, although even later administration may be beneficial.[1][27] Give further doses every 4 hours by mouth or nasogastric tube. If the patient is vomiting, try giving smaller doses every 2 hours instead and consider an anti-emetic.[1]

Once the severe clinical features of toxicity have resolved, or the high digoxin plasma concentration has reduced, stop giving the activated charcoal. Also stop if the patient has evidence of an ileus. Review the patient after 4 doses have been given.[1]

Primary options

activated charcoal: children: 1 g/kg orally every 4 hours, maximum 50 g/dose; children ≥12 years of age and adults: 50 g orally every 4 hours

ONGOING

stable after initial treatment

1st line – prescription of alternative drug and discontinuation of digoxin

2nd line – digoxin dose adjustment and regular monitoring

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Digoxin toxicity

acute, acute on chronic, or chronic toxicity

supportive care

observation for hyperkalaemia ± correction

Adults

Children (under 12 years)

observation for hypokalaemia ± correction

observation for hypomagnesaemia ± correction

digoxin-binding therapy

Practical tip

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

atropine or temporary pacing wire

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

activated charcoal

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

stable after initial treatment

prescription of alternative drug and discontinuation of digoxin

digoxin dose adjustment and regular monitoring

Digoxin toxicity

Treatment algorithm

acute, acute on chronic, or chronic toxicity

supportive care

observation for hyperkalaemia ± correction

Adults

Children (under 12 years)

observation for hypokalaemia ± correction

observation for hypomagnesaemia ± correction

digoxin-binding therapy

Practical tip

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

atropine or temporary pacing wire

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

activated charcoal

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

stable after initial treatment

prescription of alternative drug and discontinuation of digoxin

digoxin dose adjustment and regular monitoring