Journal Article•
Radioimmunoassay for serum digitoxin concentration: methodology and clinical experience.
01 Nov 1970-Journal of Pharmacology and Experimental Therapeutics (American Society for Pharmacology and Experimental Therapeutics)-Vol. 175, Iss: 2, pp 352-360
TL;DR: A reliable estimate of serum digitoxin concentration, considered in the clinical context, has been found to be useful in arriving at acute management decisions.
Abstract: A rapid radio immunoassay technique has been developed for the determination of serum digitoxin concentration in the range encountered clinically. Unlabeled digitoxin in the unknown sample competes with a tritiated digitoxin tracer for binding sites of high affinity rabbit antibodies to a human serum albumin-digoxin conjugate (average intrinsic affinity constant for digitoxin, 5.3 x 108 M-1). Free labeled digitoxin is separated from the antibody-bound fraction by adsorption to dextran-coated charcoal. The entire procedure is carried out in whole serum, obviating the problems of extraction of the drug prior to assay. The method is sensitive (2 ng/ml or less), precise (standard deviation for replicate samples ±5%), specific (no false positives in patients not receiving cardiac glycosides) and requires only one hour for completion. Six patients with electrocardiographic evidence of digitoxin intoxication had a mean serum digitoxin concentration of 34 ng/ml (S.D.6, range 26-43) which differed significantly (P ≤.001) from the mean of 17 ng/ml (S.D. 8, range 3-39) in 52 nontoxic patients. The mean age of 71 years in toxic patients tended to be greater than that of the nontoxic group (P ≤.05), whereas sex, weight, serum potassium concentration, daily maintenance digitoxin dosage and renal function as judged by blood urea nitrogen values were not significantly different. A higher incidence of coronary artery disease was found in the toxic compared with the nontoxic group (P ≤.05). A reliable estimate of serum digitoxin concentration, considered in the clinical context, has been found to be useful in arriving at acute management decisions.
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510 citations
TL;DR: Of patients who experienced cardiac arrest as a manifestation of digitalis toxicity, 54% survived hospitalization and 14 patients with adverse events considered to possibly or probably have been caused by Fab; the most common events were rapid development of hypokalemia and exacerbation of congestive heart failure.
Abstract: One hundred fifty patients with potentially life-threatening digitalis toxicity were treated with digoxin-specific antibody fragments (Fab) purified from immunoglobulin G produced in sheep. The dose of Fab fragments was equal to the amount of digoxin or digitoxin in the patient's body as estimated from medical histories or determinations of serum digoxin or digitoxin concentrations. The youngest patient received Fab fragments within several hours of birth, and the oldest patient was 94 years old. Seventy-five patients (50%) were receiving long-term digitalis therapy, 15 (10%) had taken a large overdose of digitalis accidentally, and 59 (39%) had ingested an overdose of digitalis with suicidal intent. The clinical response to Fab was unspecified in two cases, leaving 148 patients who could be evaluated. One hundred nineteen patients (80%) had resolution of all signs and symptoms of digitalis toxicity, 14 (10%) improved, and 15 (10%) showed no response. After termination of the Fab infusion, the median time to initial response was 19 minutes, and 75% of the patients had some evidence of a response by 60 minutes. There were only 14 patients with adverse events considered to possibly or probably have been caused by Fab; the most common events were rapid development of hypokalemia and exacerbation of congestive heart failure. No allergic reactions were identified in response to Fab treatment. Of patients who experienced cardiac arrest as a manifestation of digitalis toxicity, 54% survived hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)
348 citations
TL;DR: The data indicate that knowledge of the serum digoxin concentration, weighed in the clinical context, is useful in the management of patients receiving this drug.
Abstract: A radioimmunoassay for serum digoxin concentration has been used to study the interrelationships of circulating levels of the drug and various factors in the clinical setting in 48 hospitalized patients with cardiac rhythm disturbances due to digoxin intoxication. 131 patients on maintenance doses of digoxin without toxicity and 48 patients with equivocal evidence of digoxin excess were also studied and compared with the toxic group. Patients with cardiac rhythm disturbances due to digoxin intoxication tended to be older and to have diminished renal function compared with the nontoxic group; body weight, serum potassium concentration, underlying cardiac rhythm, and nature of cardiac disease were not significantly different for the groups as a whole. Despite comparable mean daily digoxin dosages, digoxin intoxicated patients had a mean serum digoxin concentration of 3.7 +/-1.0 (SD) ng/ml, while nontoxic patients had a mean level of 1.4 +/-0.7 ng/ml (P < 0.001), 90% of patients without evidence of toxicity had serum digoxin concentrations of 2.0 ng/ml or less, while 87% of the toxic group had levels above 2.0; the range of overlap between the two groups extended from 1.6 to 3.0 ng/ml. Patients with atrioventricular block as their principal toxic manifestation had a significantly lower mean serum digoxin concentration than those in whom ectopic impulse formation was the chief rhythm disturbance. Patients with equivocal evidence of digoxin excess had received comparable daily maintenance doses of digoxin but had a mean serum concentration of 1.9 +/-0.8 ng/ml, intermediate between those of the nontoxic (P < 0.005) and toxic (P < 0.001) groups. Renal function as judged by mean blood urea nitrogen concentration was also intermediate. The data indicate that knowledge of the serum digoxin concentration, weighed in the clinical context, is useful in the management of patients receiving this drug.
321 citations
TL;DR: It is concluded that the use of purified digoxin-specific Fab fragments is a safe and effective means to reverse advanced, life-threatening digitalis intoxication.
Abstract: Purified Fab fragments of digoxin-specific antibodies obtained from sheep were used to treat 26 patients with advanced, life-threatening digoxin (23 cases) or digitoxin (3 cases) toxicity. These patients had advanced cardiac arrhythmias, and in some cases hyperkalemia, which were resistant to conventional treatment. All patients had an initial favorable response to doses of Fab fragments calculated (in most cases) to be equivalent, on a molar basis, to the amount of cardiac glycoside in the patient's body. In four patients treated after prolonged hypotension and low cardiac output, death ensued from cerebral or myocardial hypoperfusion. In one case the available Fab fragment supply was inadequate to reverse a massive suicidal ingestion of digoxin, and the patient died after recurrent ventricular arrhythmias. In the remaining 21 patients, cardiac rhythm disturbances and hyperkalemia were rapidly reversed, and full recovery ensued. There were no adverse reactions to the treatment. We conclude that the use of purified digoxin-specific Fab fragments is a safe and effective means to reverse advanced, life-threatening digitalis intoxication.
275 citations
156 citations