Cholinesterase Test
Note: this site is for informational purposes only. To view test results or book a test, use the NHS app in England or contact your GP.
A cholinesterase test measures cholinesterase enzyme levels in a blood sample to assess the activity of enzymes that help regulate nerve signalling. It is used to investigate exposure to organophosphate pesticides or nerve agents and to help assess liver function, as cholinesterase levels can fall in certain liver conditions.
Why get tested?
To find out if you are likely to have temporary paralysis (known as suxamethonium apnoea) after being given a muscle relaxant called suxamethonium during surgery.
To screen for exposure to organophosphate pesticides.
When to get tested?
If you or a close relative have experienced suxamethonium apnoea after a surgical operation.
If organophosphate pesticide poisoning is suspected, for example occupational exposure in agricultural or organic chemistry industry workers.
Sample required?
A blood sample taken from a vein in your arm. This should be collected in an EDTA tube to allow measurement of red cell acetylcholinesterase activity and/or plasma cholinesterase activity. It should be sent to the laboratory as soon as possible.
Test preparation needed?
Screening should be performed prior to surgery if there is a personal or family history of suxamethonium apnoea, or after full muscle strength has returned following a surgical episode. Baseline cholinesterase measurement may be required in individuals at risk of organophosphate exposure. Comparison of baseline against samples collected after potential exposure will help confirm whether organophosphate poisoning has occurred. This may require collecting a baseline sample weeks after exposure to pesticides and anticholinergics has stopped.
What is being tested?
There are two similar cholinesterase enzymes in the body; butyrylcholinesterase (pseudocholinesterase) found in the blood plasma and acetylcholinesterase found in red blood cells. The acetylcholinesterase enzyme breaks down acetylcholine (a chemical involved in the transmission of signals across nerve endings) to prevent overstimulation of the nerves. Suxamethonium mimicks acetylcholine at nerve junctions, preventing the acetylcholine from stimulating the nerves, and is given as a muscle relaxant in anaesthetics during some surgical operations. The enzyme butyrylcholinesterase metabolises suxamethonium (and another surgical muscle relaxant mivacurium).
Genetic variation means that some individuals have a genetic abnormality making them deficient in the butyrylcholinesterase enzyme. They experience prolonged paralysis (can’t move) and apnoea (can’t breathe) after an operation since they are unable to break down suxamethonium or mivacurium very quickly. Prolonged mechanical ventilation may be required to support breathing after an operation. This is often only diagnosed after an unexpectedly prolonged response to suxamethonium or mivacurium after the operation, including during a caesarean section. Other conditions can change the enzyme activity but deficiency is usually due to gene mutations. Individuals with deficient butyrylcholinesterase enzyme have no other symptoms aside from a heightened sensitivity to muscle relaxants.
Organophosphosphate pesticides are absorbed through the skin, lungs, and gastrointestinal tract. When they bind to red blood cell acetylcholinesterase they stop this enzyme from working and this leads to a build-up of acetylcholine in nerves and associated toxicity. The speed, duration and type of symptoms of acetylcholine inhibition are dependent on the pesticide and route of exposure (but is typically 3 – 12 hours, although it can last for days). Symptoms include vomiting, paralysis and coma. Organophosphates can also bind to and inhibit butylcholinesterase but the clinical importance of this is less well known. Occupational exposure is most common, but other exposures are possible e.g. eating contaminated food.
Butyrylcholinesterase enzyme activity, biochemical phenotype and genotype are all measured in specialist laboratories. Low total enzyme activity in the blood suggests either an atypical enzyme variant which would make that individual susceptible to suxamethonium / mivacurium or acute exposure to organophosphate pesticides. Enzyme inhibitor studies are used to determine the biochemical phenotype. This involves incubating the enzyme under standardised conditions with inhibitory agents such as dibucaine and fluoride and assessing the percentage of the enzyme activity that remains (referred to as a ‘number’). The enzyme activity and phenotype together can be used to give a risk / degree of suxamethonium sensitivity and need for family studies. Genetic (DNA) studies may be useful in giving more detailed information, for example if an ‘atypical’ variant is difficult for the laboratory to identify or if a silent S gene is suspected.
Common questions
- Cholinesterase activity and phenotype studies in a patient can be used to predict the likelihood and degree of post-operative paralysis following the use of the normally short acting muscle relaxants suxamethonium or mivacurium. Dose reduction and greater care with these agents are required if deficiency is identified, so individuals are issued with drug warning cards.
- To monitor exposure to organic phosphorus compounds in the agricultural and chemical industries.
- Pre-operative screening for cholinesterase activity and phenotype is advised if the individual or a close family member has experienced prolonged paralysis after an operation that required ventilation support for several hours after surgery.
- People using specific agents linked to human poisoning including both carbamate (methomyl and aldicarb) and organophosphate (parathion, fenthion, malathion, diazinon, and dursban) insecticides in the farming or chemical industries may be routinely monitored to assess exposure once baseline levels are established. Cholinesterase activity can also be used to assess acute exposure to these compounds which can cause neuromuscular damage.
- Butyrylcholinesterase enzyme activity, biochemical phenotype and genotype may all contribute to interpretation of results.
- Low total enzyme activity in the blood suggests either an atypical enzyme variant which would make that individual susceptible to suxamethonium / mivacurium or acute exposure to organophosphate pesticides.
- The degree of sensitivity to suxamethonium varies according to the patient’s phenotype. Enzyme inhibitor studies are used to determine the biochemical phenotype. This involves incubating the enzyme under standardised conditions with inhibitory agents such as dibucaine and fluoride and assessing the percentage of the enzyme activity that remains (referred to as a ‘number’).
- The enzyme activity and phenotype together can be used to give a risk / degree of suxamethonium sensitivity and need for family studies. Classifications include: ‘usual’ (normal), ‘intermediate’, ‘atypical’ and ‘silent’. The risk of paralysis in individuals with a ‘usual’ phenotype is extremely rare whereas ‘atypical’ or ‘silent’ phenotypes may experience prolonged paralysis (e.g. 2 – 3 hours).
- Warning cards are issued to individuals with likely suxamethonium sensitivity, which should be shown prior to future surgery, as well as recommendations on family screening.
- Following exposure to organophosphate compounds, serum cholinesterase can fall to about 40% before any symptoms occur and up to 70–80% before the symptoms become severe. Direct measurement of red blood cell acetylcholinesterase activity indicates the degree of toxicity, and sequential measurement could be used to assess treatment response. It may also be useful in assessing long-term / occupational exposure. This is not widely available. Butyrylcholinesterase is more easily available but may not correlate with severity of poisoning and cannot be used to guide treatment.
- Genetic (DNA) studies may be useful in giving more detailed information, for example if an ‘atypical’ variant is difficult for the laboratory to identify or if a silent S gene is suspected.
Total cholinesterase enzyme activity can also be lowered in a number of other conditions. Temporary / other causes for decreased enzyme activity should be excluded. These include pregnancy, renal disease, shock, malnutrition, electrolyte abnormalities, neuromuscular disease, medications (e.g. chronic oral contraceptives), burns, anaemia, decompensated heart disease, age and some cancers. These are unlikely to cause severe enzyme deficiency.
As cholinesterase is synthesised by the liver the activity can also be lower in some liver diseases such as acute and chronic hepatitis, advanced cirrhosis and liver metastases. However, normal levels can be found in mild hepatitis and cirrhosis as well as obstructive jaundice.
There may be a risk of a very mild prolonged reaction to suxamethonium in these conditions (minutes as opposed to hours) due to lower activities of the usual enzyme rather than the atypical enzyme variant. If these conditions resolve, enzyme activity will return to normal.
No. It should be tested if the individual or close family member has experienced post-operative paralysis requiring ventilation or if someone has been potentially exposed to organophosphosphate chemicals, for example in the workplace.
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 any surgical team in the future to enable the anaesthetist to give a safe muscle relaxant for you.
The phenotype is determined by measuring the response of the butyrlycholinesterase enzyme to a range of enzyme inhibitors.
These are the cholinesterase genes inherited by someone from their parents. This can be determined in the laboratory using DNA techniques (genetic analysis). Butyrylcholinesterase deficiency shows autosomal recessive inheritance.