Massive digitalis toxicity and toxic digoxin levels in plasma./nClinical background: Are there any

Fråga: Massive digitalis toxicity and toxic digoxin levels in plasma. Clinical background: Are there any cases documented in the literature where plasma concentration of digoxin has reached above 8 nmol/l and where the patient has recovered? Could the maximum digoxin concentration be calculated in an intoxicated patient only having one sample taken five days after intoxication? (For further information concerning the patient we refer to Drugline question nr 11668).

Sammanfattning: There are several case reports in the literature where the level of digoxin has reached above 8 nmol/l and where the patient has recovered. We can also confirmed this in our own laboratory here at Huddinge hospital where several plasma samples with digoxin levels above 8 nmol/l in patients have been analysed. Many of the patients have recovered.

With respect to this case, it is not possible to calculate the maximum digoxin concentration in a patient with a single plasma sample above 8 nmol/l taken some days after intoxication and without knowing more data about the patient.

Svar: In a retrospective study (1) of 5100 patients on digoxin to determine the mortality rate with a four-week follow up after digoxin levels measured, a significant increase in mortality correlated with an increasing serum digoxin level. One third of the patients who died had levels above 7.7 nmol/l (from 1972 to 1980) and 15.4 nmol/l (from 1980 to 1982) at the time of death. Eleven patients had levels of more than 7.7 nmol/l, and their four-week mortality rate was 50 per cent. None had a clinical diagnosis of digoxin toxicity.

In one case report (2), the digoxin concentration reached 11.9 nmol/l and was verified by repeated analysis. Digoxin concentrations thereafter decreased rapidly over the next several hours to 5.1 nmol/l, then slowly to 1.3 nmol/l. The patient recovered. In the earlier Drugline answer (3), we referred to an article in the New England Journal of Medicine (4) in which 26 cases of advanced intoxication were reported. In 18 of these cases, the serum digoxin level was above 8 nmol/l (in many cases more than 20 nmol/l), and in 16 of these cases the patients recovered.

An earlier Drugline answer (5) referred to a case where a 78-year-old male ingested 7.5 mg digoxin. The digoxin plasma concentration reached 18.4 nmol/l; despite this fact, the patient did recover.

However, the level of the electrolytes (especially the potassium value) as discussed in the previous drugline question (3) has to be considered as the most important factor in cases of toxicity. Also, differences in the technical procedures of the analysis have to be considered. In the present case, we do not know by which method the sample is measured.

Considering the question of calculating the maximum digoxin concentration in a patient only having one sample above 8 nmol/l taken five days after intoxication, this type of calculation is not possible to do. A population based calculation could, however, be done if we have more information concerning the patient with regard to age and kidney function and with an exact value (not above 8 nmol/l). This type of calculation is, however, approximate. A more precise value of the half-life of digoxin in this patient could be calculated with at least two digoxin values.