Serum digitalis measurements in the assessment of digitalis resistance and sensitivity

Antibodies to digitalis glycosides have been elicited in experimental animals and have been utilized in the development of rapid, sensitive, specific and convenient radioimmunoassay methods for the clinical measurement of digoxin and other cardiac glycosides in man. The use of these assay methods has supplemented earlier studies with radiolabeled digitalis preparations and has made it possible to obtain much new information concerning factors which may contribute to the well known patient to patient variability in digitalis dosage requirements and in sensitivity to the toxic effects of cardiac glycosides. In some patients with a poor clinical response to digitalis, the finding of a serum concentration which is relatively low for the dose prescribed may suggest that true digitalis resistance is not present and may raise questions of poor patient compliance, tablet inadequacies, intestinal malabsorption, increased metabolic degradation or hyperthyroidism; if the cause of the low serum level cannot be identified or corrected, serial serum measurements should enable safe and rational upward adjustment of dosage. In some patients with digitalis toxicity, the finding of a serum level which is relatively high for the dose prescribed may suggest that the patient is not sensitive to digitalis but rather is excreting it slowly; in such instances in elderly patients (with decreased glomerular filtration rates) and in patients with renal disease, serial digitalis measurements are useful adjuncts to clinical observation in determining optimal digitalis dosage schedules.A knowledge of serum digitalis concentrations should enable us to develop sound principles for a more rational approach to the clinical administration of cardiac glycosides, especially in patients with unusually high dosage requirements or with unusual sensitivity to relatively small doses of digitalis.     

Correlative studies of serum digitalis levels and the arrhythmias of digitalis intoxication

Correlative studies of serum digoxin levels, cardiac rhythm and related clinical laboratory data were carried out in 114 patients. Seventy-three patients who presented with 79 episodes of arrhythmias typical of digitalis intoxication could be separated into a normokalemic group of 55 patients whose serum digoxin level was 6.68 +/- 0.17 ng/ml (mean +/- standard error of the mean), and a hypokalemic group of 24 with a mean serum digoxin level of 1.13 +/- 0.04 ng/ml (P less than 0.001). Of 45 consectutive normokalemic patients with a high serum digoxin level (more than 2 mg/ml) who underwent serial studies, 17 had arrhythmias. Serial studies in 10 hypokalemic patients revealed an inconsistent relation between presence of arrhythmia and serum digoxin level. During repletion of serum potassium in seven of these patients with an arrhythmia, the arrhythmia disappeared without a significant change in serum digoxin level in four patients. A group of seven patients had 16 episodes of serum digoxin level greater than 2.2 ng/ml, but an arrhythmia occurred during only 3 of these episodes. A sharp border between toxic and therapeutic serum digoxin values was not found in these groups of study patients. The serum digoxin level at which arrhythmias occurred appeared to be variable for both groups and individual patients. However, correlative studies utilizing serum digoxin levels can define existing thresholds for therapeutic and toxic effects and may often be more useful than isolated observations.     

Newer concepts of digitalis

Recent experiments, both elaborate and simple, performed in normal subjects and in cardiac patients with normal sized hearts emphasize the primary myocardial action of digitalis in increasing contractile tension, some effect being noted even after small doses. The drug is an important part of management of patients undergoing intracardiac surgery and in treatment of selected patients with heart block following pacemaker control of their ventricular rate. Digoxin and digitoxin are metabolized and excreted differently. Digoxin is more completely absorbed from the gastrointestinal tract than previously thought and the route of administration makes little difference on blood levels after one to two hours. There are some new notions on drug therapy for digitalis overuse.     

Eosinophilia due to the administration of digitalis

Eosinophilia apparently due to the administration of digitalis is reported. Similar cases in the literature are cited. Observations have been made on the effect of adrenalin, atropine, and pilocarpine on the eosinophile count. Eosinophilia as an effect of vagus stimulation is briefly discussed. Studies of the blood of 9 other fully digitalized patients revealed no abnormal eosinophilia.