What is Halothane Toxicity?
Halothane is a clear, heavy, odorless liquid with a sweet smell. It’s a specific type of chemical known as an alkane. The main use for halothane has been as a type of anesthesia that you breathe in. When it was introduced in 1956, it quickly took the place of older anesthetics, like ether and chloroform. One of the reasons for this is that halothane is associated with a lower risk of nausea and vomiting than other similar anesthetics.
Thanks to its side effect profile, halothane quickly became the standard in most operating rooms and was used to compare other anesthetics as they were introduced. Even though there are some issues with using halothane, such as its potential to be harmful to the liver, it is not flammable and is generally easy to administer. This led to its widespread use until the 1990s when sevoflurane became more popular.
Even so, out of all the remaining anesthetics still in use that are not ethers, halothane is the most common. It is also the most soluble, meaning that it has the greatest mix of inhaled anesthetic to brain concentration. You might think this would make halothane safer, but it is also the most powerful of the inhaled anesthetics.
There are some common side effects of halothane, including issues with the heart and blood circulation systems (low blood pressure, slow heartbeat), making the heart more receptive to irregular beating caused by adrenaline-like substances, as well as mild liver dysfunction. Irregular heartbeats are especially common in newborns and children after getting halothane, particularly a slow heart beat (bradyarrhythmias). Halothane may also cause liver damage, which is either a temporary, mild injury that gets better on its own (type 1) or severe liver damage that can lead to liver failure, which can often be deadly (type 2).
What Causes Halothane Toxicity?
Halothane is a type of medicine that is often not used in wealthier, developed countries. But in less wealthy countries or underserved areas, there may not be other options available, which means halothane toxicity, or harm from this medicine, can still be a problem.
People who are obese or have a condition called non-alcoholic fatty liver disease, which is when fat builds up in the liver, are more likely to have problems with their liver function. Because of this, they’re also more likely to have halothane toxicity. Aside from the increased risk due to existing liver problems, halothane also builds up in fat tissue. So, it takes longer for these individuals to get rid of halothane from their bodies, which might make them more likely to experience harmful effects.
There is some evidence that suggests halothane-induced liver injuries are associated with a mismatch between the supply and demand of oxygen in the body. For example, studies in rats showed that certain conditions can lead to a similar kind of liver damage as halothane.
There’s also a genetic aspect to halothane toxicity. Some studies found that people may metabolize, or break down, halothane differently based on their genetics. In other words, the amount of halothane that gets broken down in one person’s body might be quite different from the amount that gets broken down in another’s, due to genetic differences. A report of three women who were closely related suggested that genetics could play a role in how likely someone is to develop halothane toxicity.
Risk Factors and Frequency for Halothane Toxicity
Hepatotoxicity, which means damage to the liver, is a relatively common side effect of an anesthetic called halothane. It’s a major reason why its use is decreasing so fast. This liver damage has two types; the first type occurs in 20% to 30% of cases. The second type, which is more serious and is a form of hepatitis, was found to happen in 1 out of every 6000 to 20000 cases. Fatal reactions happen around once in every 35000 patients who have had just one exposure to halothane. But this risk goes up to about 1 in 1000 patients when they’ve been exposed to halothane multiple times.
To put this in perspective, there’s only ever been one confirmed case of hepatotoxicity from a different anesthetic called desflurane, and just 2 cases per 1 million with another one called enflurane. By the 1970s, halothane was the main drug causing liver failure.
- Halothane-induced liver damage affects twice as many women as men.
- Younger patients are less likely to experience it – 80% of cases are in patients who are over 40 years old.
- Other factors that increase the risk include obesity and existing liver dysfunction.
- Certain medications like phenobarbital, alcohol, and isoniazid can also increase the risk.
In a study involving 50 children, where they were given either halothane or enflurane during normal breathing, they found a 72% incidence of abnormal heart rhythms in those given halothane and 32% in those given enflurane. Of these abnormal rhythms, 41.3% were from the ventricles (lower chambers of the heart) in the halothane group, compared to only 2.8% in the enflurane group.
Signs and Symptoms of Halothane Toxicity
Halothane is a drug used in medicine that can unfortunately sometimes cause liver damage. There are two types of liver damage, or hepatotoxicity, associated with halothane. Type 1 and Type 2.
Type 1 halothane hepatotoxicity can happen with or without having been exposed to halothane before. It is seen in 20 to 30% of patients and is indicated by a rise in serum aminotransferases after surgery. This type of liver damage is usually without symptoms. However, some patients may experience symptoms such as nausea, fever, and lethargy which can appear within hours after surgery. These symptoms are typically temporary and fade on their own within 1 to 2 weeks.
Type 2 halothane hepatotoxicity, also called hepatitis, is very serious and can lead to liver cell death and liver failure, and has a high death rate. Most patients (75%) present with a mix of symptoms including yellowing of the skin and eyes (jaundice), enlarged liver, fever, loss of appetite, muscle pain, nausea, a widespread rash, and altered mental status. The hallmark presentation of this type of liver damage is a mixture of a high fever, tender enlarged liver, and jaundice starting two to three days after being exposed to halothane.
- Type 1 halothane hepatotoxicity:
- Can occur with or without previous exposure to halothane
- Occurs in 20-30% of patients
- Usually without symptoms, though some may experience:
- Nausea
- Fever
- Lethargy
- Symptoms emerge within hours after surgery and fade within 1-2 weeks
- Type 2 halothane hepatotoxicity:
- Leads to liver cell death and liver failure
- High death rate
- Symptoms emerge 2-14 days after exposure:
- Jaundice
- Enlarged liver
- Fever
- Loss of appetite
- Muscle pain
- Nausea
- Rash
- Altered mental status
Testing for Halothane Toxicity
Dysfunction in the liver after an operation can stem from various causes. That’s why it’s often challenging to pin such issues directly on ‘halothane,’ a general anesthetic. Before suspecting halothane, other common reasons like infection, low blood pressure, or side effects from other medications need to be disregarded.
To identify if halothane is causing liver dysfunction, your doctor will need to carry out a thorough check-up and collect your medical history. After that, they’ll need to run some lab tests. They might ask for a complete blood count, which could show an overwhelming presence of certain white blood cells or eosinophils, if it’s indeed a case of halothane hepatotoxicity. Also, they will check the levels of serum transaminase and bilirubin in your blood, which could be higher in most cases of halothane-induced liver problems. Usually, serum transaminase levels go back to normal in one or two weeks even without any treatment, especially if the problem is type 1 hepatotoxicity.
In some cases, patients might produce antibodies in response to liver protein byproducts called ‘trifluoroacetyl (TFA).’ These halothane-related antibodies can be identified by a test known as an enzyme-linked immunosorbent assay. If you show a positive result for these antibodies, it could confirm the suspicion of halothane hepatotoxicity.
Moreover, a liver biopsy might be performed. This diagnostic procedure involves extracting a small tissue sample from your liver for examination. If this reveals widespread destruction of liver cells in the central areas of your liver’s lobules, it could indicate halothane-induced liver damage. Do note, though, this isn’t a definitive sign. Around 40% of those with halothane-induced liver issues show an abundance of eosinophils, suggesting that their immune system is reacting to the medication. In severe cases, this can lead to acute liver failure and brain dysfunction due to the inability of the liver to eliminate toxins from the blood (hepatic encephalopathy), along with elevated serum aminotransferase levels. If your liver is already failing severely, other tests that don’t directly point to the cause might turn up abnormal results, like prolonged prothrombin time (a test that measures how long it takes blood to clot) or the international normalized ratio (a measure of blood clotting).
According to one study that looked at children who developed halothane-induced liver problems, six out of seven had detectable halothane-related antibodies. This occurrence is quite similar to adults, suggesting that this approach can be used for diagnosing both age groups.
Treatment Options for Halothane Toxicity
Halothane hepatitis is a condition that can only be diagnosed once other forms of hepatitis have been ruled out. The initial treatment for this illness is largely the same as other types of severe hepatitis and involves supportive care, which will vary from person to person. Such supportive care may involve:
- Maintaining a healthy fluid and salt balance in the body
- Correcting blood clotting problems
- Managing low blood sugar
- Providing breathing support
- Supporting the healthy functioning of the heart and blood vessels
- Giving oral lactulose and limiting protein intake
Treating halothane hepatotoxicity, a condition where the liver is damaged by halothane exposure, mostly entails providing supportive measures. There is not a lot of evidence to support the use of glucocorticoids (a type of steroid) in these cases. However, some instances show that patients improved after starting on glucocorticoids, so these steroids are still being used in some cases.
Type 2 halothane hepatitis is severe and requires close observation if suspected. The supportive care for these patients is more intensive and needs to start immediately. A liver transplant is usually required once severe liver failure is inevitable, despite the best supportive measures.
What else can Halothane Toxicity be?
The yellowing of the skin and eyes after surgery, also known as postoperative jaundice, might have a number of possible causes. These can include:
- Complications associated with general surgery
- Issues with bile-duct surgery or complications from it
- Sepsis, a severe infection that impacts the body’s response to it
- Hepatotoxicity from other drugs, which means damage to the liver caused by medication
- Hemolysis, a condition where red blood cells break down faster than they can be produced
- Viral hepatitis, an inflammatory condition of the liver
- Hypoxic hepatic injury, which refers to liver damage due to lack of oxygen
Because of these possibilities, diagnosing Halothane hepatitis, a type of liver inflammation caused by an anesthetic gas, is done by ruling out other possible causes first.
In terms of clinical studies comparing the onset of Halothane hepatitis with liver inflammation caused by other inhaled substances, there aren’t many. This is mainly because there’s already comprehensive data from animal studies, particularly in rats, on the harmful side effects of Halothane. These studies, conducted in the 1980s, help to explain how Halothane causes injury, and are often cited in medical literature on the topic.
What to expect with Halothane Toxicity
The outlook for people with type 1 halothane hepatotoxicity, a form of liver damage caused by a certain anesthetic, is fairly good. This condition typically gets better on its own over several weeks and often leaves little or no lasting damage in most cases.
On the other hand, type 2 halothane hepatotoxicity can be much more serious. If it progresses to acute liver failure, a condition where the liver stops working quickly, there’s a 50% chance of fatality. This increases to 80% if it leads to hepatic encephalopathy, a loss of brain function that happens when the liver can’t remove toxins from the blood.
If acute liver failure continues to get worse, an urgent liver transplant, a surgery that replaces a diseased or failing liver with a healthy one, is required.
Possible Complications When Diagnosed with Halothane Toxicity
Halothane, a type of anesthetic, is known for its potential to cause two types of liver damage: Type 1 and Type 2. Type 1, which is less serious, can increase certain liver enzymes in the blood and cause mild symptoms that will typically go away on their own. In contrast, Type 2, can cause severe liver disease, sudden liver failure, and a raised chance of death. Halothane can also cause heart instability, which is especially concerning for children.
Common Side Effects:
- Increased liver enzymes (Type 1)
- Mild symptoms that typically resolve on their own (Type 1)
- Severe liver disease (Type 2)
- Sudden liver failure (Type 2)
- Raised chance of death (Type 2)
- Heart instability, particularly in children
Preventing Halothane Toxicity
People often don’t get much information about the specific medicines used during anesthesia, so it’s hard for them to prevent any potential negative side effects. Halothane, a medication used for anesthesia, can sometimes cause hepatitis (liver inflammation). The main thing that will determine if a patient might get these side effects is being exposed to Halothane in the past.
Other factors that can increase the chances of experiencing side effects include prior exposure to the drug, being obese, and having a certain genetic make-up. To lessen these risks, it’s crucial to learn about ways to manage your weight and be aware of your personal and family medical history before you have to use Halothane for any medical procedures.
