What is Cardioactive Steroid Toxicity?
Cardioactive steroids (CAS) are a type of medicine that has been used for a long time to treat conditions like swelling and an old disease called “dropsy.” Some writings from the 17th century even mention their healing effects. Lots of plants have cardioactive steroids in them, like oleander, foxglove, lily of the valley, red squill, dogbane, and the common milkweed plant. For instance, the leaves of the Digitalis lanata plant contain a cardioactive steroid called digoxin, while the seeds of the Digitalis purpurea might contain one called digitalin. Interestingly, some herbal medications and enhancers from China may also contain these compounds. There is even a theory that the choice of yellow in Van Gogh’s paintings may have resulted from exposure to digitalis.
Out of all the cardioactive steroids, digoxin is probably the most well-known. Doctors use it to treat congestive heart failure (a condition where the heart can’t pump enough blood to the rest of the body) and manage the speed of ventricular rate (which basically means the pace of heartbeats) in atrial tachyarrhythmias (irregular, usually rapid heart rate that causes poor blood flow). You can take digoxin in a tablet or liquid-filled capsule, which might make your body absorb more of the medicine. There are also other cardioactive steroids like lanatoside C, digitoxin, ouabain, gitalin, and deslanoside, but they aren’t used as commonly.
What Causes Cardioactive Steroid Toxicity?
Digoxin is a medication used to treat certain heart conditions. However, if too much digoxin is taken, it can become toxic, and this usually happens in two ways: acute and chronic toxicity.
Acute toxicity often happens suddenly due to mistakes in medication dosage, intentional overdoses, and accidental consumption of plants containing similar substances to digoxin, known as CAS.
On the other hand, chronic toxicity happens over a prolonged period. It is generally caused by interactions with other drugs, certain health conditions that affect how the drug binds to proteins resulting in an increased level of free CAS, changes in how the drug is absorbed in the gut, and problems with the kidneys that affect how the drug is removed from the body. People who are very young or old, and those with kidney problems are particularly susceptible to CAS toxicity.
It is also possible to experience CAS toxicity from eating certain plants and animal products. These include plants like the Nerium oleander, lily of the valley, foxglove, and red squill. There are also certain teas and herbal products that could potentially cause CAS toxicity. In addition, secretions from the Bufo toad, sometimes used for their alleged aphrodisiac effects, contains a toxin called bufotoxin that can cause toxicity if ingested. Lastly, a herbal medicine known as Ch’an Su, which is used for heart failure and contains bufadienolides, can also cause a similar type of toxicity.
Risk Factors and Frequency for Cardioactive Steroid Toxicity
Digoxin toxicity is a widespread issue given its use in medical treatments. Additional cases have occured due to ingestion of oleander plants. There were 1,376 cases of cardiac glycoside poisoning, a condition linked to digoxin toxicity, reported in the United States in 2011. Reports of poisoning from yellow oleander leaves in India and Sri Lanka have also been documented. In South India and Sri Lanka, the consumption of Cerbera manghas fruits has resulted in cases of fatal self-poisoning.
Signs and Symptoms of Cardioactive Steroid Toxicity
CAS toxicity can cause a range of symptoms that affect different parts of the body. These symptoms can occur in cases of both acute (short-term, severe) and chronic (long-term, ongoing) toxicity. However, these signs are typically more difficult to spot in cases of chronic CAS toxicity. The symptoms can be split into two categories: non-cardiac and cardiac.
Non-cardiac symptoms can appear just minutes to hours after acute toxicity, starting with a phase when no symptoms are present. The earliest signs often involve the stomach and digestive system, such as feeling sick, throwing up, or experiencing abdominal pain. There might also be neurological symptoms, ranging from feeling weak all over to experiencing confusion. In cases of chronic toxicity, these neurological symptoms can become more severe and include feeling lethargic, disoriented, or drowsy, having headaches, seeing things that aren’t there (hallucinations), and in rare cases, experiencing convulsions. Other possible symptoms of chronic toxicity include vision problems like double vision, sensitivity to light, blind spots, seeing flashing lights, and changes in color vision.
In cases of acute toxicity, individuals may experience high potassium levels in the blood (hyperkalemia), which could have serious implications on health outcomes. Extremely high potassium levels (more than 5.5 mEq/L) can be lethal, while levels between 5.0 and 5.5 can be associated with a 50% chance of death. However, it’s important to note that high potassium levels are an indicator of the severity of CAS toxicity, but lowering these levels alone does not improve chances of survival.
Cardiac symptoms can occur due to CAS toxicity disrupting the normal functioning of the heart. Any type of irregular heart rhythm can result from the blockage of the AV node by CAS. In addition to this, if eagerness or heightened automatic function of the heart is seen at the same time as poor connection through the SA or AV node, this may indicate CAS toxicity. However, it’s worth noting that increased heart rhythm that goes back and forth in a predictable pattern (bidirectional ventricular tachycardia) is usually indicative of CAS toxicity.
If young and generally healthy individuals experience CAS toxicity, they are more likely to experience slow or irregular heart rhythms (bradydysrhythmias). In contrast, older individuals or those with pre-existing heart conditions are more likely to experience abnormal heart rhythms originating from the ventricles (ventricular dysrhythmias) or extra heartbeats (ectopy). The most common type of heart rhythm abnormality seen in CAS toxicity is AV junctional blockade with increased ventricular automaticity.
In patients taking digoxin for a long period, their ECG may display certain features such as scooped ST-segment depression (often referred to as “Salvador Dali’s mustache” appearance), inversions or flattening of the T-wave, shortening of the QT interval, and amplified U waves. Keep in mind that these ECG features suggest long-term digoxin use rather than acute toxicity.
Testing for Cardioactive Steroid Toxicity
If you’ve accidentally taken too much of certain heart medications like digoxin or digitoxin, doctors will conduct tests when you arrive to the hospital and again over six hours after you took the medicine. This is because it takes some time for these drugs to spread through your body, so a test done at least six hours after you’ve taken the drug provides a more accurate understanding of how your body is being affected.
If your doctor suspects you’ve been unintentionally taking too much of the drug over an extended period, they may need only one test to understand the situation. Levels above 2 ng/ml for digoxin and above 40 ng/ml for digitoxin six hours after taking your dose could mean there’s too much of the drug in your system.
Your doctors will also check your body’s electrolyte (salty substances in your body that carry an electric charge) levels and kidney health. They’re particularly looking for cases where your potassium or magnesium levels might be too low, as this can contribute to the damage the heart drugs can do.
They might also test for levels of acetaminophen (a common pain reliever and fever reducer) if they believe you might have taken too much of that as well, as it can initially cause very subtle harm. Finally, they’ll continuously monitor your heart with an EKG machine to spot any abnormal heart rhythms as soon as they happen so they can start treatment immediately.
Treatment Options for Cardioactive Steroid Toxicity
When someone overdoses, the first priority is to ensure that their airway, breathing, and circulation are stable. If the person has arrived quickly after the overdose, decontamination could be done to remove the harmful substance from their stomach. It’s also important to monitor and manage any abnormal heart rhythms, electrolyte imbalances, and to measure the digoxin concentration in the blood. Digoxin-specific antibody fragments are used to treat acute overdoses of the heart medication, digoxin.
Activated charcoal may be used to absorb the poison if the patient arrives one to two hours post-ingestion, on condition that the patient is awake and has control over their breathing. Administering several doses of activated charcoal can be beneficial since digoxin undergoes enterohepatic circulation, a process where the substance circulates from the gut to the liver and then back to the gut. The dose of activated charcoal is 1 mg/kg orally, and this can be given every 2 to 4 hours, up to four times. By doing so, enterohepatic circulation of digoxin is prevented, reducing its blood levels. Cholestyramine and colestipol, medicines that bind to certain substances in the intestine, may also help lessen the reabsorption of digoxin in the gastrointestinal tract.
Administering digoxin-specific antibody fragments as antivenom early in the treatment is crucial in managing acute overdoses. The criteria for initiating this medication include dangerous heart rhythms, high potassium levels in acute ingestions, non-digoxin heart medication toxicity, chronic digoxin toxicity with altered mental state, significant GI symptoms, or unusually high digoxin levels. On the other hand, high digoxin levels in patients without symptoms don’t necessarily call for the start of this medication.
The amount of DigFab (digoxin-specific antibody fragments) to be given depends on the availability of data regarding the patient’s ingested digoxin amount and blood levels. Not having these details, an estimated dose of 10 vials in adults and 5 vials in children is doable. But in very young children, careful attendance to possible volume overload is needed. If the intake amount is known, the number of vials could be calculated using a specific formula. Similarly, if digoxin levels are known, another formula could be used.
Electrolyte imbalances play a significant role in digoxin toxicity, whether it’s high or low potassium levels. High potassium levels, in particular, speak more about the severity of the digoxin toxicity rather than leading to death itself. On the other hand, if there are low potassium levels, this needs to be corrected as it escalates digoxin toxicity. In this case, low magnesium could also accompany and hence need to be replenished.
For symptomatic slow heart rate or slow heart rhythms, atropine could be administered; and fluid loss leading to hypotension can be managed with intravenous fluids. Lidocaine and phenytoin are also beneficial for managing fast ventricular heart rhythms secondary to certain cardiac medications.
Both decreased oral intake and using diuretics can increase the drug’s toxicity by reducing its excretion rate via the kidneys. So it’s important to correct any fluid deficits, improve a patient’s oral intake, and reconsider any medications contributing to fluid loss such as diuretics and laxatives.
All patients with symptoms of digoxin toxicity should be admitted to the hospital for continuous heart monitoring. Those with lethal arrhythmias, unstable vitals, or clinically significant pre-existing conditions may need intensive care.
Continual monitoring of digoxin and potassium levels along with EKG monitoring to identify arrhythmias is important. The frequency of EKG monitoring should be more often if there are abnormalities. Patients who have suspected digoxin toxicity but are otherwise asymptomatic with normal examination and lab results need to have cardiac monitoring for about 6 hours. If repeat digoxin levels are going down and the clinical course is improving, they may be safely discharged with follow-up instructions.
What else can Cardioactive Steroid Toxicity be?
There are certain conditions, both related and unrelated to toxins, that might seem like digoxin toxicity.
The conditions related to toxins that can show up like digoxin toxicity might include overdoses of calcium channel blocker, beta-blocker, and clonidine. These conditions can cause slower heart rate and low blood pressure, which are also symptoms of a digoxin overdose. A test that shows high levels of digoxin can lead us towards a diagnosis of digoxin toxicity. An overdose of calcium channel blocker can cause high blood sugar whereas a clonidine overdose can cause difficulty in breathing, slow response to stimuli, and smaller pupils. However, these characteristics alone should not be used to rule out digoxin toxicity.
Non-toxic conditions that might look like digoxin toxicity include low body temperature, an underactive thyroid, heart attack, irregular heartbeat, and high potassium levels.
People with poor kidney function, excess fluid in the body, and increased need for increased heart contractions might have high digoxin levels because of substances in their body that react with digoxin tests. These substances can be from within the body or can be taken in from outside sources like certain medicines such as spironolactone, potassium canrenone, and some Chinese herbal medicines. These substances can interfere with measuring the amount of digoxin in the body. But this interference can be avoided by measuring digoxin levels in protein-free filtered parts of the blood.
What to expect with Cardioactive Steroid Toxicity
If patients with digoxin toxicity are treated correctly, they tend to have a positive outcome. Digoxin toxicity occurs when there is too much of the heart medication, digoxin, in your body causing negative effects. Hyperkalemia, or high potassium levels in your blood, is a crucial factor in predicting the outcome.
In a study examining patients with digoxin toxicity, all patients with potassium levels above 5.5 mEq/L passed away. However, no fatalities occurred in the group with potassium levels less than 5 mEq/L. The death rate was 50% when potassium levels were between 5 to 5.5 mEq/L.
If patients with long-term digoxin toxicity are not treated, the death rate can vary from 5 to 13%. Also, as the digoxin levels in the blood increase, it might lead to increased mortality. So, regular monitoring of the levels of both potassium and digoxin is important while taking this medication.
Possible Complications When Diagnosed with Cardioactive Steroid Toxicity
It’s important to keep an eye out for heart rhythm disorders and imbalances in the amount of certain substances in the body, which may occur with CAS overdose. As the CAS affects the part of the heart that helps to control its rhythm, irregular heartbeats may be noticed. These imbalances in the body can include too much potassium, too little potassium, or too little magnesium in the blood. The patient may also experience CNS depression, which is a decreased level of consciousness. This can happen either because of the direct harmful effects of CAS or due to reduced blood flow to the brain. Though it is very rare, a condition called mesenteric ischemia, where there is poor blood supply to the intestines, can also occur.
Possible Complications:
- Heart rhythm disorders
- Imbalances in the body substances
- Too much potassium in the blood
- Too little potassium in the blood
- Too little magnesium in the blood
- Decreased level of consciousness (CNS depression)
- Reduced blood flow to the brain
- Poor blood supply to the intestines (mesenteric ischemia) – though very rare
Preventing Cardioactive Steroid Toxicity
Before starting long-term treatment with a medicine called digoxin, it’s important that patients are taught about the potential risks by their doctor or pharmacist. These risks can include accidental overdoses and unwanted reactions with other drugs. It is advised that patients do not try to “catch up” by taking a missed dose if their next dose is due within 12 hours, as this could be dangerous.
For children, and their parents, it is also essential to be informed about the toxic potential of certain plants like nerium oleander and lily of the valley. Ingesting these plants can have harmful effects, similar to digoxin overdose.
