Pharmacology & Poisoning
A 75 year old man is brought to the Emergency Department by his family. He lives alone and has mild cognitive impairment. He has a past medical history of atrial fibrillation for which he is prescribed digoxin. In a confused state he has taken multiple digoxin tablets, he cannot be certain how many. Which of the following is an indication for digoxin-specific antibody (Fab) fragments in digoxin toxicity?
Answer:
Digoxin specific antibodies are the treatment of choice for severe bradyarrhythmias and for life-threatening ventricular arrhythmias; the antidote effect is usually seen within 15-30 minutes of administration; repeated doses may be necessary depending on the clinical features. Digoxin specific antibodies are also the treatment of choice for severe hyperkalaemia (e.g. K+ greater than 6.5 mmol/L) resistant to conventional treatments.Digoxin Toxicity
Pharmacology & Poisoning
Last Updated: 25th August 2022
The therapeutic concentration of digoxin is 1 - 2 microgram/L. Plasma digoxin concentrations do not correlate well with features of toxicity in poisoning. Signs and symptoms of digoxin toxicity become more frequent with plasma concentrations above 2 microgram/L. Severe toxic effects may be seen with digoxin concentrations greater than 4 microgram/L.
The effects of digoxin may be potentiated by co-ingestion of a number of medications, including quinidine, erythromycin, verapamil, diltiazem and amiodarone. Electrolyte disturbance (hypokalaemia, hypercalcaemia, hypomagnesaemia) may also predispose the patient to digitalis toxicity.
Poor prognostic factors include: age over 55 years, male, underlying heart disease, high degree atrioventricular block, and hyperkalaemia.
Clinical features
- General features (may develop within 1 -2 hours of acute overdose)
- Nausea, vomiting, diarrhoea and general malaise
- CNS features
- Anorexia, headache, weakness and rarely blurred vision or alteration in colour perception (classically xanthopsia)
- Cardiac effects (may take 6 hours or more to develop)
- Marked bradycardia, hypotension, arrhythmias
- Metabolic effects
- Hyperkalaemia (common in severe poisoning), metabolic acidosis
N.B. Onset of features in toxicity from chronic therapy can be very variable, but is often preceded by dehydration from other causes or drug interactions. While hyperkalaemia is a useful marker of toxicity in acute overdose, it is less useful in chronic poisoning, as its absence does not indicate lack of toxicity.
ECG changes
- Digitalis effect
- Downsloping ST depression with characteristic ‘sagging’ appearance
- Flattened, inverted or biphasic T waves
- Shortened QT interval
- Digoxin toxicity
- Acute overdose usually causes a marked bradycardia with PR and QRS prolongation.
- Sinus arrest, varying degrees of AV block with dissociation or escape rhythms may occur, including paroxysmal atrial tachycardia with AV block, junctional tachycardia, frequent ventricular ectopics and bigeminy.
- In cases of severe toxicity ventricular tachycardia and ventricular fibrillation may occur.
Management
- In cardiac arrest
- Treat hyperkalaemia, collect sample for digoxin concentration, urgently administer digoxin-specific antibody FAB fragments as IV bolus
- For acute ingestions
- To reduce absorption, consider activated charcoal (charcoal dose: 50 g for adults; 1 g/kg for children) if the patient is symptomatic, or has ingested 20 micrograms/kg or more digoxin, or ingested any amount of a toxic plant, provided the airway can be protected and gut motility is normal (N.B. even late administration of activated charcoal may be beneficial when this substance is ingested in overdose)
- In patients who are symptomatic, or who have ingested 20 micrograms/kg or more digoxin, or who have ingested any amount of a toxic plant:
- Give further doses of activated charcoal to increase elimination from plasma, provided the patient’s airway can be protected and gut motility is normal
- Give activated charcoal (50 g for adults; 1 g/kg for children) every 4 hours by mouth or nasogastric tube. If vomiting is a problem, smaller amounts of charcoal hourly or every 2 hours may cause less gastric irritation. Consider an antiemetic e.g. cyclizine (IV 50 mg for adults; 0.5-1 mg/kg for children) or ondansetron (slow IV 4-8 mg for adults; 0.1 mg/kg for children)
- Stop oral activated charcoal if any of the following criteria are met:
- There is evidence of ileus.
- Severe clinical features and/or high plasma concentration have resolved.
- Review need for activated charcoal after 4 doses (including initial dose to prevent absorption, if administered), and sooner if clinical features resolve or exposure is less severe.
- Monitor vital signs and cardiac rhythm; check the capillary blood sugar; perform a 12 lead ECG; check U&Es and magnesium
- Digoxin concentration should be measured at least 6 hours post-ingestion; samples for digoxin do not need to be measured urgently unless features of severe toxicity are present and treatment with digoxin specific antibodies is being considered
- Observe all patients who require assessment for at least 6 hours after ingestion
- Hyperkalaemia
- Treat severe hyperkalaemia conventionally
- Digoxin specific antibodies are the treatment of choice for severe hyperkalaemia (e.g. K+ greater than 6.5 mmol/L) resistant to conventional treatments
- Hypokalaemia
- Correct hypokalaemia to the high end of normal with oral or intravenous potassium supplementation
- Arrhythmias
- Digoxin specific antibodies are the treatment of choice for severe bradyarrhythmias and for life-threatening ventricular arrhythmias; the antidote effect is usually seen within 15-30 minutes of administration; repeated doses may be necessary depending on the clinical features
- If digoxin specific antibodies are not immediately available for managing severe bradycardia and AV block give atropine intravenously, 1.2 mg for an adult or 0.02 mg/kg for a child; repeat doses may be necessary
- Metabolic acidosis
- If metabolic acidosis persists despite correction of hypoxia and adequate fluid resuscitation consider correction with intravenous sodium bicarbonate
- Hypotension
- Ensure adequate fluid resuscitation; treat brady and tachyarrhythmias appropriately; consider early referral to critical care for patients with fluid-resistant hypotension, as these patients can deteriorate extremely rapidly
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
