What is a normal digoxin level

Digoxin is derived from the leaves of the foxglove plant (Digitalis species plant). Digoxin is a type of medicine called a cardiac glycoside. Digoxin helps make the heart beat stronger and with a more regular rhythm. Digoxin is currently used as an inotrope to improve systolic dysfunction in patients with congestive heart failure and as an atrioventricular nodal blocking agent for managing atrial tachydysrhythmias ¹. Digoxin is prescribed to alleviate some symptoms of heart failure. Digoxin strengthens the contractions of the heart and helps it to pump blood more efficiently. Digoxin also helps control the heart rate and abnormal heart rhythms known as arrhythmias. Digoxin will not cure heart failure or arrhythmias, which are chronic conditions, but can help to manage the symptoms along with diet, exercise, and other medications. Digoxin may improve the quality of life in heart failure patients, but it does not provide a mortality benefit.

Digoxin is prescribed to treat heart failure, a long-term, chronic condition. It will not cure heart failure but will help to control it. You may have to take digoxin — and have tests to monitor its level in the blood — for the rest of your life.

Digoxin levels must be monitored because the drug has a narrow safety range. If the level in the blood is too low, symptoms may recur. If the level is too high, toxicity may occur. Digoxin dosage may be adjusted based on levels measured.

• Therapeutic digoxin level: 0.5 to 2.0 nanograms/mL (1.02 to 2.56 nanomol/L). But the right level for some people may vary depending on the situation.
• Toxic digoxin level: greater than 2.4 nanograms/mL (3.07 nmol/L)

Timing of the digoxin blood test is important because if the sample is drawn too soon after a dose, the results of the test may be erroneously high and will show a toxic level when that is not the case. Many times, the blood sample will be drawn just before the next dose is to be taken.

Digoxin toxicity can present acutely, by an intentional or accidental overdose, or chronically, such as when patients on digoxin develop worsening renal function. Similar toxicity can occur after exposure to cardioactive steroids in plants such as oleander, red squill, or dogbane or from animals such as Bufo toads ².

Digoxin’s therapeutic half-life is between 30 to 40 hours, but this may change in overdose. Digoxin excretion is primarily renal, and for this reason, patients with poor or worsening renal function, such as patients who are elderly or have chronic kidney disease (end-stage renal disease), are more likely to develop digoxin toxicity. Digoxin levels start to plateau at 6 hours, which is after tissue redistribution has occurred; earlier levels may thus be misleadingly high. Cardiovascular toxicity may have delayed manifestation of up to 8 to 12 hours post ingestion.

Digoxin exhibits its therapeutic and toxic effects by poisoning the sodium-potassium ATPase. The subsequent increase in intracellular sodium leads to increased intracellular calcium by decreasing calcium expulsion through the sodium-calcium, cation exchanger. Higher intracellular calcium increases inotropy which can be of symptomatic benefit in congestive heart failure. At toxic levels, automaticity can be increased as well. Digoxin also increases vagal tone by decreasing dromotropy at the AV node. This can be used to control atrial tachydysrhythmias.

Digoxin level test

A healthcare practitioner will order the digoxin test to measure digoxin at the beginning of drug therapy to ensure correct dosage. The main purpose of digoxin test is to determine the best dosage of digoxin and prevent side effects. It is important to monitor the level of digitalis medicines such as digoxin. That is because the difference between a safe treatment level and a harmful level is small.

Digoxin takes approximately one to two weeks to reach a steady level in the blood and in the target organ, the heart. A digoxin test done at that time will reflect more accurately whether a person is receiving the right amount of digoxin.

Once the dosage level is determined, routine monitoring of digoxin levels, at a frequency determined by the healthcare practitioner, will verify correct dosage.

A digoxin test may be ordered when it is suspected that levels are too low in someone who is taking the medication and has symptoms of heart failure, such as:

• Fatigue
• Shortness of breath
• Swelling in the hands and feet (edema)

Digoxin test may be ordered when toxicity is suspected and the affected person has signs and symptoms such as:

• Dizziness
• Blurred vision or seeing yellow or green halos
• Vomiting
• Diarrhea
• Irregular heartbeat
• Difficulty breathing
• Loss of appetite

Changes in health status can affect levels of digoxin and its ability to control symptoms. Digoxin tests may be done, and the dose adjusted if necessary, when someone experiences a physiologic change that may affect blood levels and effectiveness of digoxin, for example, kidney or thyroid problems, cancer, or stomach or intestinal illness.

Normal Results

For congestive heart failure, the ideal range of levels of digoxin in the blood, known as the therapeutic range, may be between 0.5 and 0.8 nanograms/mL. Each person’s response to medications is different. Many factors, including kidney function and concurrent medications, may be involved. If someone’s symptoms do not improve or if the person is experiencing side effects, then the healthcare provider may need to adjust the digoxin dose up or down according to that person’s needs.

The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results.

Therapeutic ranges have not been established for patients who are less than 16 years of age.

Abnormal Results

Abnormal results may mean you are getting too little or too much digoxin.

A very high value could mean that you have or are likely to develop a digoxin overdose (toxicity).

Toxic concentration: >4.0 ng/mL (levels of 4.0 ng/mL and above may be potentially life-threatening).

Digoxin toxicity

Approximately 1% of heart failure patients treated with digoxin develop toxicity ¹. Additionally, 1% of adverse drug effects in patients greater than age 40 are due to digoxin toxicity; the incidence rises to greater than 3% in patients over age 85. Plant ingestions account for 80% of pediatric exposure; the remaining 20% of pediatric ingestions arise from medications ¹. In general, ventricular dysrhythmias are more common in the elderly whereas supraventricular dysrhythmias are more common in children.

Prescription drugs that can interact with digoxin include: quinidine, flecainide, verapamil, amiodarone, amiodarone, azole antifungals (such as itraconazole, ketoconazole), cyclosporine, lapatinib, macrolide antibiotics (such as clarithromycin, erythromycin), propafenone, ranolazine, rifampin, and ciprofloxacin. Herbal remedies such as St. John’s wort, oleander, and lily of the valley may affect levels of digoxin in the blood. Eating licorice may also affect blood levels of the drug.

Digoxin is primarily cleared from the system by the kidneys. When someone has kidney problems, the person’s healthcare provider may want to monitor kidney function and blood potassium levels since kidney dysfunction and low levels of potassium can result in symptoms of digoxin toxicity.

Digoxin toxicity can be aggravated by potassium and magnesium levels, so a healthcare provider may monitor electrolytes and other ions like magnesium as well.

In cases where toxic levels of digoxin are found, a healthcare practitioner may administer a specialized antidote (digoxin immune FAB) to reverse the effects of the digoxin.

Digoxin toxicity causes

Digoxin toxicity can be caused by high levels of digoxin in your body. A lower tolerance to the drug can also cause digoxin toxicity. People with lower tolerance may have a normal level of digoxin in their blood. They may develop digoxin toxicity if they have other risk factors.

People with heart failure who take digoxin are commonly given medicines called diuretics. This drugs remove excess fluid from the body. Many diuretics can cause potassium loss. A low level of potassium in the body can increase the risk of digoxin toxicity. Digoxin toxicity may also develop in people who take digoxin and have a low level of magnesium in their body.

You are more likely to have this condition if you take digoxin, digitoxin, or other digitalis medicines along with drugs that interact with it. Some of these drugs are quinidine, flecainide, verapamil, and amiodarone.

If your kidneys do not work well, digoxin can build up in your body. Normally, it is removed through the urine. Any problem that affects how your kidneys work (including dehydration) makes digoxin toxicity more likely.

Some plants contain chemicals that can cause symptoms similar to digoxin toxicity if they are eaten. These include foxglove, oleander, and lily of the valley.

Digoxin toxicity pathophysiology

Increased intracellular calcium from the poisoning of the Na-K transporter and AV nodal blockade from increased vagal tone are the primary causes of digoxin toxicity. The former leads to increased automaticity and inotropy; the latter leads to decreased dromotropy. Hyperkalemia can be a marker of severe toxicity in acute poisoning. The role of potassium is less clear in chronic toxicity, although it has been linked to higher mortality despite traditional teaching that hypokalemia worsens the dysfunction at the Na-K transporter ³.

Digoxin toxicity symptoms

These are symptoms of digoxin toxicity:

• Confusion
• Irregular pulse
• Loss of appetite
• Nausea, vomiting, diarrhea
• Fast heartbeat
• Vision changes (unusual), including blind spots, blurred vision, changes in how colors look, or seeing spots

Other symptoms may include:

• Decreased consciousness
• Decreased urine output
• Difficulty breathing when lying down
• Excessive nighttime urination
• Overall swelling

Gastrointestinal upset is the most common symptom of digoxin toxicity. Patients also may report visual symptoms, which classically present as a yellow-green discoloration, and cardiovascular symptoms, such as palpitations, dyspnea, and syncope. Elderly patients frequently will present with vague symptoms, such as dizziness and fatigue. The most important historical detail in evaluating a random digoxin level is the time of the last dose.

A classic but uncommon side effect of digoxin is the appearance of yellow halos around lights, called xanthopsia, and altered color vision, called chromatopsia.

Digoxin toxicity diagnosis

Your health care provider will examine you. Your heart rate may be rapid, or slow and irregular. For patients with acute digoxin toxicity, it is critical to obtain an ECG to check for irregular heartbeats, a basic metabolic panel, and digoxin levels on arrival. These tests should be repeated at 6 hours post ingestion. Digoxin effect on the ECG is characterized by diffuse scooping of the ST segments which can be seen with therapeutic levels and is not associated with toxicity. The most common ECG abnormality is frequent premature ventricular contractions (PVCs), although the “pathognomonic” ECG finding is bidirectional ventricular tachycardia. However, this has been reported in aconitine poisoning ⁴.

Blood tests that will be done include:

• Blood chemistry
• Kidney function tests, including blood urea nitrogen (BUN) and creatinine
• Digitoxin and digoxin test to check levels
• Potassium level
• Magnesium level

In the setting of acute overdose, acetaminophen and aspirin levels can help screen for occult overdose.

In chronic toxicity, the cause of toxicity should be sought. Common causes include infection, renal failure, and accidental overdose. Serum digoxin levels do not always correlate with toxicity given variable tissue levels and other factors affecting digoxin’s toxicodynamic effects.

Digoxin toxicity treatment

If the person has stopped breathing, call your local emergency number, then start CPR.

If the person is having trouble breathing, call your local emergency number.

At the hospital, symptoms will be treated as appropriate.

Digitoxin blood level may be lowered with repeated doses of charcoal, given after gastric lavage.

Methods to cause vomiting are usually not done because vomiting can worsen slow heart rhythms.

In severe cases, medicines called digoxin-specific antibodies (DSFab) may be prescribed. Dialysis may be needed to reduce the level of digitalis in the body.

Calcium is traditionally considered contraindicated in hyperkalemic patients with digoxin toxicity for fear of ‘stone heart syndrome,’ an irreversible state of global myocardial contraction. This is based on animal evidence and case report, but more recent literature found no evidence of increased mortality with calcium administration. In general, hyperkalemia in the setting of digoxin toxicity should be treated primarily with digoxin-specific antibody fragments (DSFab) fragments if available.

Digoxin-specific antibody fragments

Digoxin-specific antibody binding fragments (DSFab), brand name Digibind or Digifab, are an effective antidote that directly binds digoxin.

Digoxin-specific antibody fragments is indicated for life-threatening toxicity including:

• Ventricular arrhythmias
• High-grade heart blocks
• Hypotension
• Symptomatic bradycardia
• Potassium greater than five meq/L in acute overdose
• Acute ingestions greater than 10 mg in an adult or greater than 4 mg in a child
• Digoxin Concentration greater than 15 ng/mL measured at any time
• Digoxin Concentration greater than 10 ng/mL measured 6 hours post ingestion.

Empiric dosing of digoxin-specific antibody fragments (DSFab) can be given at a dose of ten to 20 vials for critically ill patients after acute overdose, three to six vials for chronic toxicity in adults, or one to two vials for chronic toxicity in children.

Digoxin-specific antibody fragments (DSFab) also can be dosed as follows ¹:

• (0.8 times the ingested dose)/0.5 = Number of vials of Digoxin-specific antibody fragments (DSFab) for acute overdose
• (Digoxin level (steady state) x Weight [kg])/100 = Number vials of Digoxin-specific antibody fragments (DSFab) for acute or chronic overdose

Digoxin-specific antibody fragments (DSFab) also can be given for poisoning with natural toxins, but the dosing is unclear.

The typical digoxin-specific antibody fragments (DSFab) infusion is over 30 minutes, but it may be given as a bolus for critical patients. The onset of effect is approximately 20 minutes, with complete effect usually seen within 90 minutes.

Care should be taken to completely reverse digoxin in patients who are chronically taking digoxin, as reversal may exacerbate their underlying disease. These patients should be closely monitored afterward for the same reasons.

If digoxin-specific antibody fragments (DSFab) is not available, then treatments such multidose-activated charcoal, atropine, and antidysrhythmics such as phenytoin or lidocaine may be employed. Cardioversion and pacing may induce dysrhythmias and are typically not used, but they may be needed in patients without other therapeutic options.

Dialysis also may be indicated in the patient with acute renal failure or refractory hyperkalemia; however, it is not useful as a treatment for digoxin toxicity itself.

Disposition depends on the patient’s symptoms and stability as well as their potassium and digoxin levels.

Many analyzers cannot measure free digoxin concentrations, and in this setting, digoxin levels should not be followed after administration of DSFab.

In patients with the end-stage renal disease, dissociation of the DSFab-digoxin complex may occur and cause recurrent toxicity.

References

1. Cummings ED, Swoboda HD. Digoxin Toxicity. [Updated 2019 May 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470568
2. Supervía Caparrós A, Salgado García E, Calpe Perarnau X, Galicia Paredes M, García Gibert L, Córdoba Ruiz F, Clemente Rodríguez C, Nogué Xarau S. Immediate and 30 days mortality in digoxin poisoning cases attended in the Hospital Emergency Services of Catalonia, Spain. 2019 EneEmergencias. 31(1):39-42
3. Smolders EJ, Ter Horst PJG, Wolters S, Burger DM. Cardiovascular Risk Management and Hepatitis C: Combining Drugs. Clin Pharmacokinet. 2019 May;58(5):565-592
4. Cosmi F, Tarquini B, Mariottoni B, Cosmi D. [Digitalis, a drug to be scrapped?] G Ital Cardiol (Rome). 2017 Feb;18(2):121-128