Cholinesterases: Acetylcholinesterase, Pseudocholinesterase and Dibucaine Number
Synonym/Acronym
Cholinesterase: CHS; Acetylcholinesterase: AcCHS, RBC or red blood cell cholinesterase, erythrocyte cholinesterase, true cholinesterase; Pseudocholinesterase: PCHE.
Rationale
To assess for acquired or inherited pseudocholinesterase deficiency.
Patient Preparation
There are no food, fluid, activity, or medication restrictions unless by medical direction.
Normal Findings
Method: Spectrophotometry, kinetic.
| Test | Conventional Units |
|---|
| Acetylcholinesterase (AcCHS)/RBC cholinesterase | 25–50 U/g Hgb |
|
| Test | Conventional Units |
|---|
| Pseudocholinesterase (PCHE) | | | Males | 3,334–7,031 units/L | | Females | 2,504–6,297 units/L |
|
| Dibucaine Number | Fraction (%) of Activity Inhibited |
|---|
| Normal homozygote | 79%–84% | | Heterozygote | 55%–70% | | Abnormal homozygote | 16%–28% |
|
Study type: Blood collected in a red-, or lavender-top [EDTA] tube; related body system: Digestive and Musculoskeletal systems.
The cholinesterases are a group of serine hydrolase enzymes. They catalyze a chemical reaction that hydrolyzes or breaks down the neurotransmitter acetylcholine into choline and acetic acid. This reaction is necessary to allow neurons activated by acetylcholine to return to a resting state. There are two types of cholinesterase:
- Acetylcholinesterase (AChE), or “true cholinesterase,” found in red blood cells, lung, spleen, nerve endings, and the brain (gray matter). The gray matter contains the brain’s neurons and nerve synapses; neurons have three main parts—uncoated axon terminals, dendrites or receivers, and the nerve cell body. Gray matter is located in the cerebellum, cerebrum, brain stem, and a butterfly-shaped portion in the center of the spinal cord.
- Pseudocholinesterase, found mainly in plasma, liver, muscle, pancreas, heart, and brain (white matter). The white matter is composed of bundles of myelin coated axons or transmitters that send signals up and down between the brain and spinal cord to the rest of the body.
Acquired acetylcholinesterase and pseudocholinesterase deficiency is caused by exposure to carbamate and organophosphate insecticides (e.g., parathion, malathion) known to inhibit its activity. Organophosphate pesticides bind irreversibly with cholinesterase, inhibiting normal enzyme activity. Carbamate insecticides bind reversibly. Acquired pseudocholinesterase deficiency is more common than the inherited form.
Inherited pseudocholinesterase deficiency is caused by an autosomal recessive mutation in the butyrylcholinesterase (BCHE) gene. The complete DNA sequence and amino acid structure of both the normal pseudocholinesterase protein and most of its abnormal variants have now been identified and can be identified using genetic testing. The inherited deficiency occurs with a frequency of 1 in 3,200 to 1 in 5,000 people. Abnormal genotypes of pseudocholinesterase are identified using the dibucaine and fluoride inhibition tests because, in normal individuals, these chemicals inhibit pseudocholinesterase activity.
Patients with inherited pseudocholinesterase deficiency are at risk during administration of anesthesia if succinylcholine is administered as an anesthetic. Succinylcholine, a short-acting muscle relaxant, is a reversible inhibitor of acetylcholinesterase and is hydrolyzed by cholinesterase. Succinylcholine-sensitive patients may be unable to metabolize the anesthetic quickly, resulting in prolonged or unrecoverable apnea. Widespread preoperative screening is not routinely performed.
Factors That May Alter the Results of the Study
Acetylcholinesterase
- Drugs and other substances that may increase acetylcholinesterase levels include echothiophate, parathion, and antiepileptic drugs such as carbamazepine, phenobarbital, phenytoin, and valproic acid.
- Improper anticoagulant; fluoride interferes and causes a falsely decreased acetylcholinesterase value.
Pseudocholinesterase
- Drugs and other substances that may increase pseudocholinesterase levels include carbamazepine, phenytoin, and valproic acid.
- Drugs and other substances that may decrease pseudocholinesterase levels include ambenonium, barbiturates, chlorpromazine, contrast medium (iopanoic acid, iodipamide), cyclophosphamide, echothiophate, edrophonium, esmolol, estrogens, fluorides, glucocorticoids, hexafluorenium, ibuprofen, isoflurophate, metoclopramide, neostigmine, oral contraceptives, pancuronium, parathion, phenelzine, physostigmine, procainamide, pyridostigmine.
- Plasmapheresis decreases pseudocholinesterase levels.
- Pregnancy (pseudocholinesterase levels are decreased by about 30%).
Increased In
Acetylcholinesterase
- Hemolytic anemias (e.g., sickle cell anemia, thalassemias, spherocytosis, and acquired hemolytic anemias) (increased in hemolytic anemias as AChE is released from the hemolyzed RBCs)
Pseudocholinesterase
Increased levels are observed in a number of conditions without specific cause.
Decreased In
Acetylcholinesterase
Pseudocholinesterase
The enzyme is produced in the liver, and any condition affecting liver function may result in decreased production of circulating enzyme.
- Acute infection
- Anemia (severe)
- Carcinomatosis
- Cirrhosis
- Hepatic cancer
- Hepatocellular disease
- Infectious hepatitis
- Inherited deficiency
- Insecticide exposure (organic phosphate exposure decreases enzyme activity)
- Malnutrition(possibly related to decreased availability of transport proteins; condition associated with decreased enzyme activity)
- Muscular dystrophy
- Myocardial infarction
- Plasmapheresis (iatrogenic cause)
- Succinylcholine hypersensitivity(this chemical is a trigger in susceptible individuals)
- Tuberculosis(chronic infection is known to decrease enzyme activity)
- Uremia(pathological condition known to decrease enzyme activity)
Before the Study: Planning and Implementation
Teaching the Patient What to Expect
- Discuss how this test can assist in evaluating for enzyme deficiency.
- Note that symptoms of pesticide poisoning are related to the type of pesticide exposure.
- Explain that a blood sample is needed for the test.
Potential Nursing Actions
- Discuss health concerns associated with pesticide exposure causing symptoms such as blurred vision, convulsions, headaches, muscle weakness, nausea, pulmonary edema, salivation, sweating, or vomiting.
- Explain that there are no reportable symptoms of pseudocholinesterase deficiency until exposure to muscle relaxants succinylcholine or mivacurium occurs.
After the Study: Implementation & Evaluation Potential Nursing Actions
Treatment Considerations
- Observe the patient with decreased values for signs of fluid volume excess related to compromised regulatory mechanisms, decreased cardiac output related to decreased myocardial contractility or dysrhythmias, and pain related to inflammation or ischemia.
- Discuss the importance of using a medic alert bracelet to notify health-care workers of increased risk from exposure to medications that may lower cholinesterase activity.
- Facilitate support to discuss concerns related to impaired activity secondary to weakness and fear of shortened life expectancy.
- Provide education regarding access to genetic counseling services and screening tests for other family members.
- Emphasize that taking succinylcholine or mivacurium when diagnosed with pseudocholinesterase deficiency will result in muscle relaxation and affect the inability to breath independently.
- Discuss the implications of abnormal test results on the patient’s lifestyle.
- Provide education related to the clinical implications of the test results.
Clinical Judgement
- Consider how to provide emotional support for concerns related to impaired activity secondary to weakness and fear of shortened life expectancy.
Follow-Up and Desired Outcomes
- Acknowledges contact information provided regarding genetic counseling services and screening tests for other family members.
- Understands the value of using a medic alert bracelet to notify health-care workers of increased risk from exposure to medications that may lower pseudocholinesterase activity.
- Understands that depending on the results of this procedure, additional testing may be performed to evaluate or monitor disease progression and determine the need for a change in therapy.