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.
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.
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.
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.
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.