TOXBASEŽ - Updated 01/2002

 

Type of product:

Cardiac glycoside

 

Ingredients:

Digoxin
Tablets - 62.5 micrograms, 125 micrograms and 250 micrograms
Elixir - 50 micrograms/mL

 

Toxicity:

Ingestion > 0.05 mg/kg body weight (> 50 micrograms/kg) would be expected to cause a plasma digoxin level above the upper limit of the therapeutic range. The fatal dose is variable. Death has occurred after 4 mg but patients have survived ingestion of 20-40 mg with treatment. Death usually occurs from ventricular arrhythmias, conduction impairment or pump failure.

The therapeutic concentration is 0.8 - 2.2 ug/L. In acute poisoning plasma digoxin concentrations do not correlate well with features of toxicity but concentrations > 4 ug/L are often associated with severe toxic effects.

Young children tend to tolerate a higher peak plasma digoxin level than adolescents and adults. (Woolf 1992).

Risk factors for toxicity include: age > 55 years, male, underlying heart disease, high degree atrioventricular block and hyperkalaemia (Taboulet P. 1993). Patients with pre-existing acute or chronic renal failure are at greater risk of toxicity.

The plasma half-life after therapeutic doses is 20-50 hours.

Digoxin - features and management

Updated 12/2003

 

General features:

Toxic features develop within 6 hours of ingestion.

Cardiac glycosides commonly cause nausea and vomiting and sometimes diarrhoea. Other features, particularly in chronic toxicity, include anorexia, headache, general malaise, weakness, blurred vision and alteration in colour perception. Confusion, hallucinations, paraesthesia and delirium may occasionally occur.

 

Cardiac effects:

Acute overdosage usually causes a marked bradycardia with PR and QRS prolongation. Sinus arrest, varying degrees of A-V block with dissociation or escape rhythms may occur but more serious ventricular dysrhythmias are uncommon.

With chronic, or acute on chronic toxicity, any type of arrhythmia may occur. These include paroxysmal atrial tachycardia with AV block, junctional tachycardia, severe bradycardia, any degree of atrioventricular block, frequent ventricular ectopics and bigeminy. In cases of severe toxicity ventricular tachycardia and ventricular fibrillation may occur.

Arrhythmias are more common if there is pre-existing heart disease and electrolyte disturbances such as hypokalaemia.

 

Metabolic effects:

Hyperkalaemia is common in severe poisoning and a metabolic acidosis may also be present.

In cases of acute on chronic toxicity, patients may be hypokalaemic if diuretics are also being prescribed and hypokalaemia is a risk factor for digoxin induced arrhythmias in this group.

 

Management:

The benefit of gastric decontamination is uncertain.
1. Consider activated charcoal (50 g for adults; 1 g/kg for children) if an adult presents within 1 hour of ingestion of > 3000 micrograms or > 50 micrograms/kg body weight in a child. In patients receiving digoxin therapeutically this threshold should be reduced by half.

2. Consider repeated doses of oral activated charcoal, provided the patient is not vomiting and the airway can be protected. There are no controlled trials which demonstrate benefit in overdosage but evidence in volunteers does suggest it may increase the elimination of digoxin.

3. Observe the patient for at least six hours if asymptomatic.

4. Measure urea, electrolytes and creatinine in all patients.

5. Monitor pulse, blood pressure and cardiac rhythm.

6. Perform a 12 lead ECG.

7. Timing of measurement of digoxin concentration varies with clinical presentation. In severe poisoning urgent measurement is essential if digoxin specific antibodies are being considered. Samples taken to investigate chronic digoxin intoxication should be measured at least 6 hours after ingestion. Samples do not need to be measured urgently unless features of severe toxicity are present and treatment with digoxin antibodies is being considered (see below). When requesting concentrations it is important to specify digoxin, digitoxin or plant since methods vary. Repeat measurements may be required as digoxin absorption is slow.

8. Digoxin elimination is slow (half-life 16-20 hours) and frequent analysis of digoxin is unhelpful.

Metabolic
Disturbances of potassium are common in digoxin toxicity. Hyperkalaemia is a feature of severe poisoning and hypokalaemia increases the risks of arrhythmias.

8. Correct hypokalaemia with oral or intravenous potassium supplementation. In addition, measure magnesium level and correct if necessary.

9. Treat hyperkalaemia with intravenous dextrose and insulin. Avoid calcium since this increases ventricular automaticity and may precipitate ventricular arrhythmias. Consider need for digoxin specific antibodies. Discuss with your local poisons service: in the UK NPIS 0870 600 6266, in Ireland NPIC (01) 809 2566.

10. In the presence of renal failure haemodialysis may be of benefit for severe hyperkalaemia or acidosis, but potassium must be monitored repeatedly if used with Digibind since the concentration may fall rapidly.

11. Correct metabolic acidosis with 250 mL of 1.26% sodium bicarbonate i.v. in an adult and repeat as necessary (250 mL of 1.26% contains 37.5 mmol). Alternatively 50 mL of 8.4% contains 50 mmol sodium bicarbonate but caution is advised if it is to be given by a peripheral venous line as it is irritant to veins and can cause skin necrosis in cases of extravasation.

Arrhythmias
12. Correct hypokalaemia, hypomagnesaemia and acidosis which may contribute to arrhythmias

13. Give atropine intravenously, 1.2 mg for an adult or 0.02 mg/kg for a child, for marked bradycardia and atrioventricular block. Repeat doses may be necessary.

14. Consider insertion of a temporary pacing wire if there is evidence of significant bradycardia or AV block with haemodynamic compromise, and there is limited response to atropine.

15. Consider the use of digoxin specific antibodies for life threatening ventricular arrhythmias. Discuss with your local poisons service: in the UK NPIS 0870 600 6266, in Ireland NPIC (01) 809 2566.

16. Ventricular arrhythmias may also respond to intravenous magnesium, even if the magnesium level is normal. The usual dose is 8-10mmol IV bolus in an adult, repeated as necessary. (Kinlay 1995, Green 1989, Tzivoni 1990). An infusion of 4-8 mmol/ hour (1-2 g) may be required in cases of recurrent ventricular arrhythmias. If repeat doses of magnesium are required it is important to monitor the patient's magnesium level and watch for features of magnesium toxicity (neuromuscular dysfunction, respiratory compromise, loss of deep tendon reflexes).

Avoid class 1a and 1c antiarrhythmics e.g. quinidine, flecainide, disopyramide which can affect AV nodal conduction.

 

Digoxin specific antibodies (Digibind)

Digoxin antibodies have a potent binding affinity for digoxin.
Indications for use include:
* Hyperkalaemia (potassium > 6 mmol/L)
* Haemodynamically unstable arrhythmias
* Imminent cardiac arrest
* Digoxin level > 10 ug/L
* Ingestion of > 10 mg in an adult or > 0.3 mg/kg body weight in a child

Adverse effects are rare but urticaria and low platelets have been reported.

Digibind may be considered for use in pregnancy if the benefits to the mother are greater than the risk to the foetus. Discuss with your local poisons service: in the UK NPIS 0870 600 6266, in Ireland NPIC (01) 809 2566.

Clinical improvement is usually seen within 30-60 minutes of starting Digibind.

Monitor potassium regularly since concentrations may fall rapidly, particularly if dextrose/insulin or sodium bicarbonate have also been given.

Digibind interferes with digoxin immunoassays therefore digoxin levels are unreliable for 5-7 days after treatment.

The digoxin-Fab complex has an elimination half life of 19-30 hours (up to 137 hours in renal failure). Dissociation of digoxin from the antibody may lead to rebound of free digoxin and recurrence of toxic features. This is unlikely if the correct dose of Digibind has been given, but it is important to continue cardiac monitoring for at least 24 hours after treatment (and longer in cases of severe renal failure).

Converting units
ug/L(or ng/mL) x 1.28 = nmol/L
nmol/L x 0.781 = ug/L(or ng/mL)

Digibind Sources