Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Compounds in the digitalis family of glycosides consist of a steroid nucleus, a lactone ring, and a sugar. Digoxin is widely prescribed for the treatment of congestive heart failure and various disturbances of cardiac rhythm. Digoxin improves the strength of myocardial contraction and results in the beneficial effects of increased cardiac output, decreased heart size, decreased venous pressure, and decreased blood volume. Digoxin therapy also results in stabilized and slowed ventricular pulse rate. These therapeutic effects are produced through a network of direct and indirect interactions upon the myocardium, blood vessels, and the autonomic nervous system.
Digoxin is well absorbed after oral administration and is widely distributed to tissues, especially the heart, kidney, and liver. A number of factors can alter normal absorption, distribution, and bioavailability of the drug, including naturally occurring enteric bacteria in the bowel, presence of food in the gut, strenuous physical activity, ingestion of quinine or quinidine, and concomitant use of a wide range of drugs. Children generally require higher concentrations of digoxin.
After oral administration, there is an early rise in serum concentration. Equilibration of serum and tissue levels occurs at approximately 6 to 8 hours. For this reason, blood specimens for digoxin analysis should be drawn at least 6 to 8 hours after drug administration. Digoxin is excreted primarily in the urine. The average elimination half-life is 36 to 40 hours, but may be considerably prolonged in those with renal disease, causing digoxin accumulation and toxicity.
Symptoms of digoxin toxicity often mimic the cardiac arrhythmia's for which the drug was originally prescribed (eg, heart block and heart failure). Other typical symptoms of toxicity include gastrointestinal effects, including anorexia, nausea, vomiting, abdominal pain and diarrhea, and neuropsychologic symptoms, such as fatigue, malaise, dizziness, clouded or blurred vision, visual and auditory hallucination, paranoid ideation, and depression. Toxicity of digoxin may reflect several factors: the drug has a narrow therapeutic window (a very small difference exists between therapeutic and toxic tissue levels); individuals vary in their ability to metabolize and respond to digoxin; absorption of various oral forms of digoxin may vary over a 2-fold range; susceptibility to digitalis toxicity apparently increases with age.
Monitoring digoxin therapy
The therapeutic range is 0.6 to 1.2 ng/mL.
Levels of 4.0 ng/mL and above may be potentially life-threatening.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Patients vary in their responsiveness to the drug, and renal dysfunction permits accumulation of digoxin in the serum.
This assay measures both bound and free digoxin, so high values will be found in patients undergoing treatment with digibind (antibody fragment therapy).
"Digoxin-like" immunoreactive factors may cause falsely-elevated values in some neonates and patients with advanced liver or renal disease.(1)
In patients undergoing therapy with high biotin doses (>5 mg/day), do not draw specimens until at least 8 hours have elapsed since the last biotin administration.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Reference values have not been established for patients that are less than 16 years of age. In adults, the suggested serum Digoxin therapeutic range is 0.6-1.2 ng/mL.
Toxic concentration: > or =4.0 ng/mL
> =16 years
Toxic concentration: > or =4.0 ng/mL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Datta P, Hinz V, Klee G: Comparison four digoxin immunoassays with respect to interference from digoxin-like immunoreactive factors. Clin Biochem 1996;29(6):541-547
2. Applied Therapeutic Drug Monitoring. Vol 2. Edited by TP Moyer, RL Boeckx. Washington, DC, American Association for Clinical Chemistry, 1984
3. Jortani SA, Voldew R Jr: Digoxin and its related endogenous factors. Crit Rev Clin Lab Sci 1997;34:225-274
4. Dickstein K, Cohen-Solal A, Filippatos G, et al: ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Eur Heart J 2008;29:2388-2442