As a reference blood level, while the therapeutic range of digoxin is 0.5 – 1.0 ng / ml, the toxic doses are 3 mg in adults and 1 mg in children.With reference to digitalis intoxication, it is important to emphasize that potassium is always implicated in this condition, albeit in a different way in the case of intoxication during chronic treatment or acute intoxication.
In case of acute intoxication, a competition between digitalis and potassium occurs at the digitalis binding site on the cell membrane; the concomitant use of diuretics for the treatment of chronic heart failure can also cause hypokalaemia and thus increase the effects of digitalis.
In the case of chronic intoxication, however, there is a progressive increase in serum potassium levels, which can reach a fatal dose. In practice, it should be noted that digitalis can give cardiac toxic effects even at therapeutic doses if associated with hypokalaemia, while acute digitalis overdose is associated with hyperkalaemia.
Clinical manifestations of digitalis intoxication
Clinical manifestations of digitalis poisoning can be cardiac or extracardiac.Cardiac effects Extracardiac effectsAcute intoxicationVentricular ectopiasA-V block of varying degreesSenisible atropine bradiartmiaNausea, vomiting, abdominal painVertigo, confusion, drowsiness
Chronic intoxicationVentricular arrhythmiasBradyarrhythmiasAnorexia, nausea, vomiting, abdominal painDelirium, disorientation, confusionHallucinations, convulsions, visual disturbances (yellow vision)Digitalis poisoning, diagnosis
The diagnosis of digitalis intoxication is based on the anamnestic collection and on the serum dosage of the levels of digoxinaemia, taking into account that in this second case it is possible to record very high levels in the first hours of intake even in the face of a silent clinical picture, as the phase of tissue distribution can last from 6 to 12 hours.
Treatment of digitalis poisoning
Therapy and care for patients with digitalis intoxication is based on the following points:
Decontamination: gastrolusis, activated charcoal and catharsisCorrection of electrolyte changes (hypo / hyperkalemia)Administration of atropine to treat any bradyarrhythmiaAdministration of antiarrhythmic drugs in case of hyperkinetic arrhythmiasAdministration of the antidote.
The antidote for digitalis poisoningAs for the last point, the antidote is represented by antibody fragments (Fab), or antidigital immunoglobulins of ovine origin.T pharmaceutical form is represented by 40 mg vials that can be administered intravenously (eg Digifab®).
These antibodies begin their therapeutic action within the first 30 minutes of administration, with full effectiveness within 1-3 hours. Their half-life, as these antibodies have a wide tissue distribution, is very long (15-20 hours), which is further extended if the patient suffers from renal failure (up to 140 hours).
These antibodies are used as they act by forming immune complexes with circulating digitalis derivatives, for which they have high affinity, blocking their pharmacological action and related toxic effects.
The dosage of Digifab® varies according to the concentration of glycoside to be neutralized; it is therefore necessary to determine the amount of glycoside ingested or the plasma digoxin values before administering the antidote.In principle, the required dose can be calculated as follows:
Calculation of the absorbed dose
Starting from the ingested dose: Digoxin ingested dose x 0.8Starting from plasma concentration (at least 6 hours after ingestion): plasma digoxin concentration (in ng / ml or mcg / l) x 5.6 x weight (kg) / 1000
Calculation of the necessary Fabs: to obtain a complete molar neutralization it is necessary that all the circulating digitalis be chelated. For this purpose, it is necessary to administer 80 mg of Fab for each mg of absorbed digitalis.
In the event that it is not possible to estimate the ingested dose or determine the digoxinaemia and the diagnosis is certain, 40-120 mg of antidote can be administered, repeatable within 60 minutes if there is no clinical response.
In addition, in patients undergoing chronic digitalis treatment, the chelation of all circulating digitalis could precipitate a pre-existing heart failure that is being treated. It is therefore necessary to administer a lower dose of Fab compared to that required by molar neutralization.