What is Pseudocholinesterase Deficiency?
Pseudocholinesterase deficiency is a rare condition that can be inherited or acquired. It’s a defect in an enzyme produced by the liver called pseudocholinesterase. In the practice of anesthesia (administering drugs to prevent pain during surgeries), two muscle relaxants, succinylcholine and mivacurium, are often used to aid in the process of inserting a tube into the windpipe and making the surgical area more accessible.
These two drugs are broken down in the body by the pseudocholinesterase enzyme. In people with abnormal forms of pseudocholinesterase, the body is not as efficient at breaking down these two drugs. This can result in extended periods of muscle paralysis from standard doses of succinylcholine and mivacurium.
What Causes Pseudocholinesterase Deficiency?
You can get pseudocholinesterase deficiency in two ways: it can either be inherited (passed down from parents to their children) or acquired (developed because of certain conditions or medicines).
In the case of inherited pseudocholinesterase deficiency, this happens due to changes in a specific gene related to an enzyme found in our body called butyrylcholinesterase. This gene is located on a certain part of our third chromosome. Some patients may inherit only one of these changed genes, while others get two. Those with only one changed gene experience longer-lasting effects of nerve blockers (drugs that prevent nerves from sending signals), but it only increases by about 30 percent. However, those with a changed gene from both parents, can experience the effects of nerve blockers for two to three hours.
On the other hand, acquired pseudocholinesterase deficiency develops under certain health conditions or due to certain drugs. Being malnourished, being pregnant or having just given birth, having burns, liver or kidney disease, being on hemodialysis, suffering from a heart attack or heart failure, living with cancer, chronic infections, and taking medicines like steroids and cytotoxic agents can lead to less production of the pseudocholinesterase enzyme. Other medications and certain chemicals, like certain insecticides, drugs used to treat depression (known as MAO inhibitors), and drugs that block a certain enzyme (called anticholinesterase drugs) can also inhibit the functionality of the pseudocholinesterase enzyme.
Risk Factors and Frequency for Pseudocholinesterase Deficiency
Pseudocholinesterase enzyme deficiency is a condition that affects roughly 1 out of every 2000 to 5000 people who have two copies of the abnormal gene (homozygotes). For those with one abnormal gene copy (heterozygotes), the rate of incidence is about 1 out of every 500 people. Interestingly, this condition affects males twice as much as females. Certain groups have a higher likelihood of having pseudocholinesterase deficiency, including males of European descent, Persian people from the Jewish community, and some Alaska Natives.
- Pseudocholinesterase enzyme deficiency appears in 1 out of 2000 to 5000 people with two faulty genes (homozygotes).
- The deficiency shows up in approximately 1 out of 500 people with one abnormal gene (heterozygotes).
- Males are twice as likely as females to have this deficiency.
- The groups most likely to have pseudocholinesterase deficiency are males of European descent, Persian individuals within the Jewish community, and particular Alaska Natives
Signs and Symptoms of Pseudocholinesterase Deficiency
Pseudocholinesterase deficiency is usually identified when a patient experiences long-lasting muscle weakness after being administered standard doses of certain medications like succinylcholine or mivacurium. To diagnose this, doctors may ask about previous anesthesia experiences that required extended use of a ventilator due to muscle weakness. They may also ask about any family members diagnosed with pseudocholinesterase deficiency.
Individuals with certain health conditions like cancer, severe burns, heart attack, heart failure, pregnancy, liver disease, hemodialysis, and chronic infections may develop a secondary form of pseudocholinesterase deficiency. These conditions may cause reduced levels of the pseudocholinesterase enzyme, making the patient more likely to experience long-lasting muscle weakness with standard doses of succinylcholine or mivacurium. Certain medications can also decrease the activity of pseudocholinesterase, which can worsen the enzyme deficiency.
It’s important to note that there are no unique physical signs of pseudocholinesterase deficiency. People with this condition may seem perfectly healthy (if it’s inherited) or they may show signs related to their other health conditions (if it’s acquired).
Testing for Pseudocholinesterase Deficiency
In order to check for a condition called pseudocholinesterase deficiency, a sample of the patient’s blood is taken for a laboratory checklist. This test measures the activity of an important enzyme in your blood, known as pseudocholinesterase.
Dibucaine, a type of local anesthetic, is used in this test. In healthy individuals, dibucaine usually stops about 80% of the pseudocholinesterase enzyme’s activity. However, in people with a different form of pseudocholinesterase enzyme, only a smaller degree of activity is stopped by dibucaine. It’s estimated between 50 to 60% in heterozygotes (those who have one copy of the altered enzyme) and 20 to 30% in homozygotes (those who have two copies).
The level of enzyme activity stopped by dibucaine is also known as the dibucaine number. Further testing can be done to determine the exact amount of pseudocholinesterase in the sample. This is usually performed using a technique called colorimetry, which measures concentration using the absorption of light.
Treatment Options for Pseudocholinesterase Deficiency
People with pseudocholinesterase deficiency are usually diagnosed after they experience extended muscle paralysis after having standard doses of certain medications like succinylcholine and mivacurium. The main treatment for this condition is respiratory support with the help of a mechanical ventilator. This system helps the patient breathe until their own muscle function begins to recover naturally.
To regularly check if muscle function is returning, nerve stimulation is used. During this time, it’s also important that the patient stays sedated (medicine is given to make the patient relax or sleep) to reduce anxiety and the feeling of being aware yet unable to move.
The preferred treatment is to provide support with sedation (medications to help the patient relax or sleep) and mechanical ventilation (machine-assisted breathing), until recovery takes place – usually occurring within several hours. This approach is deemed to carry less risk than the alternatives, which include a transfusion of plasma (liquid part of the blood) or the use of other medications to try and reverse the paralysis. These options have previously proven to be unreliable.
For those patients who have already been diagnosed with pseudocholinesterase deficiency, the approach is to avoid using the drugs succinylcholine and mivacurium, which block nerve signals to muscles. Instead, doctors recommend using other safe alternatives for future anesthetic procedures such as atracurium, rocuronium, and vecuronium.
What else can Pseudocholinesterase Deficiency be?
When trying to diagnose pseudocholinesterase deficiency, doctors consider other conditions that might cause similar symptoms. These include:
- Overdose from narcotics
- Residual neuromuscular blockade (remaining muscle paralysis)
- Cholinergic crisis (excessive activation of the nervous system)
- Myasthenia gravis (a disorder causing muscle weakness)
- Myasthenic syndrome (another disorder causing muscle weakness)
- Hypermagnesemia (very high levels of magnesium in the blood)
- Hypophosphatemia (low levels of phosphate in the blood)
- Hypokalemia (low levels of potassium in the blood)
What to expect with Pseudocholinesterase Deficiency
Pseudocholinesterase deficiency is a health condition usually discovered only after exposure to certain drugs called succinylcholine or mivacurium. Many people might not know they have it unless they have had exposure to these drugs. If someone is diagnosed with pseudocholinesterase deficiency after being exposed to succinylcholine or mivacurium, they can fully recover. This recovery happens as muscle function naturally returns.
However, during this time, they will need mechanical ventilation – a machine to help them breathe – and close observation by their medical team. This is to prevent what’s known as hypoxic respiratory failure, a condition where the body doesn’t receive enough oxygen.
Possible Complications When Diagnosed with Pseudocholinesterase Deficiency
Pseudocholinesterase deficiency’s main complication is the inability to breathe properly due to a long-lasting muscular paralysis after being given succinylcholine or mivacurium. Continuous monitoring and the use of a mechanical ventilator is required until the patient regains muscle function on their own. Also, people with pseudocholinesterase deficiency might be at risk for sudden heart failure if they use cocaine.
Main Risk Factors:
- Long-lasting muscular paralysis resulting in breathing difficulties
- Requires continuous monitoring and breathing assistance
- Sudden heart failure from cocaine use
Preventing Pseudocholinesterase Deficiency
If you have been diagnosed with a condition called pseudocholinesterase deficiency, it’s vital to inform your doctor and the person who gives you anesthesia before any surgery. This is because your condition needs to be recorded in your medical history. Pseudocholinesterase deficiency is an inherited condition, which means it involves a gene that can pass from parents to children. This condition affects how your body responds to certain medications used during surgery.
Specifically, if you have this condition, your body can’t properly break down certain types of anesthesia drugs, like succinylcholine and mivacurium. These are medications used to relax your muscles during surgery. If these drugs are used, it could result in a longer than normal period of muscle relaxation and even breathing problems. That’s why it’s so important for doctors to know about your condition before any operation.
And because pseudocholinesterase deficiency can be inherited, it’s recommended that your family members get tested as well. This is merely a precautionary measure to ensure they are aware if they have inherited this risk, as they would need to inform their doctors too.
