Comparison of Serum Digoxin Level Measurement with Acetyl Strophanthidin Tolerance Testing

Abstract

SUMMARYSerum digoxin levels (SDL) were compared with tolerance for the rapidly acting cardiac aglycone, acetyl strophanthidin (AS). AS titration tests were performed on 133 patients with diverse cardiac disorders. All were receiving maintenance digoxin. Both exquisite AS sensitivity and tolerance for a 1.0 mg AS were associated with a wide range of SDL values. Concordance and discordance between the two methods in assessing degree of digitalization were evaluated by considering SDL of 1.4 ng/ml to be the mean value for patients without glycoside-induced cardiac arrhythmia. An SDL of <1.5 ng/ml with tolerance for 1.0 mg AS and an SDL of >1.4 ng/ml with sensitivity to 1.0 mg AS or less constituted concordant responses. An SDL of <1.5 ng/ml with intolerance for 1.0 mg or less AS and an SDL of >1.4 ng/ml with tolerance for 1.0 mg AS comprised discordant responses. In 60 of 144 (42%) AS titrations discordant results were observed. Severe pulmonic, coronary, and aortic valvular heart disease, as well as old age, contributed to unusual AS sensitivitv. Titration with AS clarified pharmacologic quantification of SDL by providing insight into optimum therapeutic glycoside dose. Development of a radioimmunoassay for digoxin promised to resolve questions concerning appropriate dosage of this commonly employed digitalis glycoside. Several studies indicated that the quantity of drug present in the serum could be determined with precision. 9 Serum digoxin concentration measurements delineated a therapeutic range of values and provided a convenient marker for differentiating toxic from nontoxic patients with cardiac arrhythmias.20' 21 Eighty-five percent of patients with manifestations suggesting digitalis intoxication showed blood levels above 2.0 ng/ml; while a similar percentage of those without evidence of overdosage had concentrations below this value.22 However, the range of overlap between toxic and nontoxic groups was wide, from 1.6-3.0 ng/ml.22 More recent reports indicate an even wider range of overlap, extending through virtually the entire serum digoxin concentration span encountered clinically.23Implicit in the clinical use of serum digoxin levels for assessing the state of digitalization are two assumptions: first, that blood levels reflect faithfully myocardial drug concentrations, and second, that a given concentration is associated with specific effect.

Diminished inotropic responses but unaltered toxicity to acetylstrophanthidin in the senescent beagle.

“…There was no age difference in the extent of inhibition expressed as a percent of total inhibition over the entire range of concentrations of the glycoside. Discussion VT, as an index of toxicity, has been used previously and the range of ACS concentrations over which VT occurred is similar in this study to that reported for other adult dogs.4 23 There was no difference in the threshold for ACS toxicity, defined as VT, in the senescent dogs compared with the adult dogs (table 1).…”

Serum Digoxin Levels in Elderly Nursing Home Patients: Appraisal of Routine Periodic Measurements

“…Therefore, while in one patient a low serum level may be an adequate indication of the control of heart failure, in another patient a higher level, sometimes in the toxic range, may be necessary. Klein and co‐workers (5) demonstrated this situation with the acetylestrophanthidin test performed in patients receiving a maintenance dose of digoxin. They showed that in 22 percent of patients with a serum digoxin level of less than 0.7 ng/ml, arrhythmia was induced by less than 0.6 mg of acetylstrophanthidin, indicating that the patients were exquisitely sensitive to digoxin.…”

Serum Digoxin Concentration and Diagnosis of Digitalis Toxicity Current Concepts

“…This overlap is most marked in prospective blinded studies, and has led some investigators to question whether knowledge of serum digoxin concentrations really enhances clinical decision-making beyond routinely available data such as renal function and body mass (Ingelfinger and Goldman, 1976). Klein et al (1974) used the rapidly acting cardiac aglycone acetyl-strophanthidin in digitalised patients to assess their ability to tolerate more digitalis. They found in 42% of cases that the digoxin concentration alone did not predict the response to incremental digitalis doses.…”

“…They found in 42% of cases that the digoxin concentration alone did not predict the response to incremental digitalis doses. Thus, many patients with serum digoxin concentrations greater than 2.0 ng/ml could tolerate more digitalis without toxicity, while others with concentrations in the 0.5 to 1.5 ng/ml range were either close to or already showing toxicity (Klein et al, 1974).…”