What is being tested?

Cholinesterases are enzymes that are involved in the proper functioning of the nervous system. There are two separate cholinesterase enzymes in the body: (1) acetylcholinesterase, found in red blood cells, lungs, spleen, nerve endings, and grey matter of the brain, and (2) butyrylcholinesterase (pseudocholinesterase) found in the serum, liver, muscle, pancreas, heart, and white matter of the brain.

Acetylcholinesterase is involved in transmission of nerve impulses by breaking down acetylcholine, a chemical that helps to transmit signals across nerve endings. A decrease in the activity of the enzyme acetylcholinesterase results in excess of acetylcholine at nerve endings. This can lead to overstimulation of nerves within body tissues and organs. Butyrylcholinesterase is involved in processing drugs. Cholinesterase tests measure the activity of these enzymes.  The two most common indications for testing cholinesterase levels in the blood are:

• Organophosphate pesticide exposure. Organophosphate insecticides can inhibit acetylcholinesterase and butyrylcholinesterase activities. Symptoms can be severe with acute exposure to these pesticides or can gradually appear with chronic exposure. Absorption can occur by inhalation, ingestion, or contact with the skin. Testing red blood cell acetylcholinesterase and serum butyrylcholinesterase may be performed to detect acute poisoning or to monitor those with occupational exposure to these chemicals, such as farm workers or those who work with industrial chemicals.
• Inherited butyrylcholinesterase deficiency. Some individuals have an inherited deficiency due to a genetic variant of the enzyme butyrylcholinesterase. This enzyme is used by the body to inactivate suxamethonium, a muscle relaxant that is commonly used during surgery. People who have low levels or defective butyrylcholinesterase may experience prolonged effects of the drug, with prolonged muscle paralysis and apnoea following anaesthesia. In addition, those who are homozygous for the genetic variants may be at greater risk of adverse effects than those who are heterozygous. Butyrylcholinesterase testing can be performed prior to surgery on individuals with a family history of prolonged apnoea after use of suxamethonium to determine if they are at risk of complications related to this drug.

Laboratory measurement of butyrylcholinesterase activity in the blood may be complemented by ‘phenotype’ studies. The phenotype studies involve incubating a person’s blood sample with a range of inhibitors such as dibucaine (‘dibucaine inhibition test’). The percentage of the enzyme activity remaining in the patient sample is referred to as a ‘number’. The laboratory can determine whether the patient has a normal or an abnormal enzyme activity. Some laboratories perform genetic (DNA) studies instead of phenotype studies. However in Australia there is currently no Medicare rebate for butyrylcholinesterase genetic studies.

How is it used?

Cholinesterase testing has two main uses:

• It can be used to detect and diagnose organophosphate pesticide exposure and/or poisoning. It may also be used to monitor those who may be at increased risk of exposure to organophosphate compounds, such as those who work in agricultural and chemical industries, and to monitor those who are being treated for exposure. The tests for red blood cell acetylcholinesterase (AChE) and serum pseudocholinesterase (PCHE) are used for this purpose.
• It can be used to determine if someone with a past history of or a family history of prolonged muscle paralysis or apnoea following the use of suxamethonium (a common muscle relaxant used for anaesthesia) is at risk of having this reaction due to butyrylcholinesterase deficiency. The test for butyrylcholinesterase activity in the blood is generally used. This may be complemented by a ‘phenotype’ test (such as dibucaine inhibition testing) or genetic (DNA) testing.

When is it requested?

• People using organophosphate compounds such as Parathion, Sarin or tetraethyl pyrophosphate in the farming or chemical industries may be routinely monitored to assess any adverse exposure once baseline levels are established. Cholinesterase levels can also be used to assess any acute exposure to these compounds which can cause neuromuscular damage. Toxicity can follow a rapid absorption of the compound through the lungs, skin or gastrointestinal tract. The symptoms of toxicity are varied, ranging from vomiting to paralysis or coma, and depend on the compound, quantity and the site of exposure.
• Pre-surgery screening for cholinesterase activity and phenotype is advised if the patient or a close family member has experienced prolonged paralysis or apnoea after a surgery, requiring ventilation support up to several hours after surgery.

What does the result mean?

In monitoring for occupational pesticide exposure:
Following exposure to organophosphate compounds, red blood cell acetylcholinesterase and butyrylcholinesterase activities can fall to about 80% of normal before any symptoms occur and drop to 40% of normal before the symptoms become severe. Those who are regularly exposed to these compounds may be monitored for toxic exposure by establishing a baseline activity level and then testing on a regular basis to watch for significant reduction in the activity of acetylcholinesterase or butyrylcholinesterase.

In testing for acute organophosphate pesticide exposure/poisoning:
Significantly decreased cholinesterase activity levels usually indicate excessive absorption of organophosphate compounds. Butytrylcholinesterase and red blood cell acetylcholinesterase activities are usually decreased within a few minutes to hours after exposure. Butyrylcholinesterase activity may regenerate in a few days to weeks, while red blood cell acetylcholinesterase activity will remain low for as long as one to three months. Butyrylcholinesterase and acetylcholinesterase regenerate at different rates since butyrylcholinesterase is produced in the liver, with a half-life of about two weeks, whereas acetylcholinesterase is produced in red blood cells, which have a lifespan of about 120 days.

In testing for suxamethonium sensitivity:
About 3% of people have low activity levels of butyrylcholinesterase due to an inherited deficiency and will have prolonged effects from the muscle relaxant suxamethonium. Total quantitative butyrylcholinesterase levels will be evaluated prior to surgery for patients with a history or family history of prolonged muscle paralysis or apnoea following use of suxamethonium. Low activity levels of butyrylcholinesterase indicate that these people may be at increased risk of experiencing prolonged effects of suxamethonium. The dibucaine inhibition test characterises the degree of a person’s sensitivity to the drug. The lower the result from a dibucaine inhibition test, the greater the risk of drug sensitivity.

Is there anything else I should know?

In addition to inherited deficiency and exposure to organophosphates, reduced cholinesterase levels can also be caused by chronic liver disease and malnutrition. It may lowered in pregnancy, kidney disease and some cancers.

If someone unexpectedly has prolonged apnoea after surgery, testing for butyrylcholinesterase should be performed at least 24 to 48 hours after you received suxamethonium.  This is important to avoid interference by the drug suxamethonium that could affect the test results.

Common questions

• Should everyone be tested for cholinesterase?

No. It should be tested if a person or a close family member has experienced post-surgery paralysis or apnoea requiring ventilation or if someone is in potential contact with organophosphate chemicals regularly in the workplace.

• What happens if I have an atypical phenotype?

The report from the laboratory will be sent to the requesting doctor and placed in your medical notes. You should also be given a medical warning card that can be shown to your surgeon or anaesthetist in the future to enable the anaesthetist to give a safe muscle relaxant for you.

• What is a cholinesterase genotype?

These are the genes for cholinesterase inherited by someone from their parents. This can be established in the laboratory using genetic (DNA) testing techniques.

• What is a cholinesterase phenotype?

This can be determined by defining the properties of the enzyme protein structure. The phenotype is derived by measuring the response of the cholinesterase enzyme in a person's blood to a range of enzyme inhibitors.

More information

RCPA Manual: Cholinesterase

RCPA Manual: Cholinesterase - red cell