A 78-year-old man is brought to emergency after her daughter found him confused.She also reported that on the drive to the hospital he complained that it was too bright outside and asked why the sky was yellow. In this potentially life-threatening emergency, can you guess the diagnosis?
A 78-year-old man is brought to the emergency department by his daughter after she found him confused. He had apparently vomited recently but had not cleaned up afterwards, which was not his usual behaviour. Since he lived alone and his daughter visited him every other day, she did not know exactly how long her father had been in this condition.
She also reported that on the drive to the hospital he complained that it was too bright outside and asked why the sky was yellow. But she was not sure if he was confused or actually saw yellow. Compared to his normally calm disposition, she perceived him to be agitated.1
In the emergency room, the patient was tachycardic and an ECG was ordered. This showed a dome shape anterolateral ST segment depression and atrial tachycardia with atrioventricular block (AV block). Laboratory results revealed hyperkalaemia. The patient’s daughter reported that the man was taking several continuous medications, but she had forgotten to bring his tablet boxes in the hurry.
The patient presented four "red flags" for intoxication with digoxin/digitoxin. It is often the case that nausea or vomiting occurs after 1-3 hours in acute poisoning, with more rare episodes of diarrhoea or abdominal pain. During this period, patients also tend to suffer neurological events of confusion or drowsiness.
After typically 4-8 hours, cardiac symptoms appear. Cardiac glycosides can trigger a wide variety of arrhythmias: ventricular extrasystoles, bradyarrhythmias, tachyarrhythmias, and even third-degree AV block (also known as complete heart block) or ventricular fibrillation (V-fib or VF). Often bradycardia initially occurs, and arrhythmias with consecutive hypotension only develop over the course of the disease. Rare but specific is the occurrence of visual disturbances, for example in the form of halos around bright objects or a disturbed colour vision (mostly of a yellow or green tint).2,3
Such poisoning can occur not only through ingestion of an overdose, but also through accumulation in renal insufficiency (in the case of digoxin) and, more rarely, through ingestion of plants containing cardiac glycosides [e.g. foxglove (genus: digitali), oleander (Nerium oleander), or lily of the valley (Convallaria majalis)].
Particularly in acute intoxications, hyperkalemia can occur, which can be dangerous, due to inhibition of the sodium-potassium ATPase enzyme (Na⁺/K⁺-ATPase). It should also be kept in mind that hyperkalemia can also be caused by errors in pre-analysis (long stasis, tapping the veins before puncture), which can sometimes lead to misdiagnosis and even the overlooking of hypokalemia.
Hyperkalemia, high-grade AV block, older age, pre-existing heart disease and male gender are associated in the relevant literature with higher mortality, as is a very high blood level. However, the determination of levels is only of limited help for two reasons: on the one hand, this is only possible 6 hours after the last intake, and on the other hand, levels of cardiac glycosides can only be regarded as a guideline: Patients with elevated levels may nevertheless be clinically unremarkable and patients with signs of poisoning may well have a normal serum level.
Disturbances of colour vision and ECG changes may occur even at therapeutic doses. In cardiac patients, levels of 10-15 ng/mL or more for digoxin or 30 ng/mL or more for digitoxin are considered to be a vital threat.2,3
There are no accepted guidelines for the management of digitoxin intoxication. In acute intoxication, a single administration of charcoal for toxin elimination up to about 2 hours after ingestion makes sense, because digoxin and digitoxin are absorbed from the digestive tract within 2-3 hours.
The most effective measure is the administration of the antidote DigiFab® (1 phial of 40 mg binds about 0.5 mg digoxin/digitoxin), even if its use and dosage are discussed inconsistently. There is agreement that it is indicated in life-threatening cardiac arrhythmias and hyperkalaemia (> 5-6 mmol/l) as well as when very large amounts of the active substance are taken.
Supportive atropine can be given for bradycardia and volumes initially for hypotension. Hypokalaemia should be corrected. Administration of magnesium (2 g magnesium sulphate 10%) may break some arrhythmias. Lowering hyperkalaemia, on the other hand, does not result in reduced mortality and can therefore be approached cautiously.2,3
References:
1. Make the Diagnosis: Why His Agitation, Confusion, and Tachycardia? https://www.medpagetoday.com/quizzes/diagnosis/91250.
2. Digitalis Intoxications - ToxDocs. http://toxdocs.de/2019/digitalis/.
3. Pocket Cards Intoxications. http://toxdocs.de/wp-content/uploads/2021/01/2021_01_03-Toxdocs-Pocket-Cards.pdf.