What Is Pseudocholinesterase Deficiency?
Pseudocholinesterase deficiency, also known as butyrylcholinesterase deficiency, is an inherited or acquired condition in which the metabolism of certain choline ester drugs such as Succinylcholine, Mivacurium, and ester-linked local anesthetics is altered.
People with a deficiency of pseudocholinesterase enzymes suffer from prolonged paralysis and apnea after administering drugs like Succinylcholine or Mivacurium. Therefore, these drugs should not be administered to patients having pseudocholinesterase deficiency.
People usually lead their entire lives with pseudocholinesterase deficiency and do not experience any adverse health hazards until they are exposed to Succinylcholine or Mivacurium, or any genetic defect is discovered.
What Is the Function of Pseudocholinesterase Enzyme?
Pseudocholinesterase is a serine hydrolase plasma enzyme that is primarily produced in the liver. It plays a role in the catalysis of the hydrolysis of choline ester drugs, most significantly Succinylcholine and Mivacurium. It is crucial to differentiate this enzyme from acetylcholinesterase which is a true cholinesterase that occurs in higher concentrations within the central or peripheral nervous systems and neuromuscular junctions.
Pseudocholinesterase primarily affects the activity of neurons, predominantly within the hippocampus, amygdala, thalamus, and other deep layers of the cerebral cortex.
The enzyme plays a pivotal role in the maturation of the central and peripheral nervous systems by regulating neuronal growth and cellular proliferation.
Pseudocholinesterase deficiency causes increased sensitivity in individuals administered with choline ester muscle relaxant medications, specifically:
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Succinylcholine.
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Mivacurium.
How Common Is Pseudocholinesterase Deficiency?
Pseudocholinesterase deficiency is a rare genetic or acquired disorder that occurs in approximately one in 3,200 to one in 5,000 people. It more commonly prevails in certain Persian Jews and Alaska Natives communities.
What Are the Acquired Conditions Affecting Pseudocholinesterase Activity?
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Liver Disease- Pseudocholinesterase enzyme is mainly synthesized in the liver. Thereby, when the liver function is affected, it leads to impaired synthesis of the enzyme pseudocholinesterase. Decreased enzyme levels have been shown in many patients affected with liver diseases, such as cirrhosis, end-stage liver disease, hepatitis, and liver abscesses.
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Renal Disease- There is an association between renal diseases and decreased pseudocholinesterase levels in the literature.
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Malnutrition- Malnutrition is also closely related to changes in serum albumin and pseudocholinesterase enzymes. This is more likely attributed to the changes in hepatic synthesis of the proteins and enzymes associated with this disease.
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Pregnancy- A considerable decrease in pseudocholinesterase activity is found in the tenth week of pregnancy. The pseudocholinesterase enzyme activity further decreases in the postpartum before coming back to normalcy between ten days and six weeks postpartum. Therefore, pregnant women should be careful about this condition. The enzymatic activity is said to be reduced by 24 % during pregnancy, 25 % on day one postpartum, and 33 % on day three postpartum, respectively. Therefore, selecting an appropriate anesthetic plan for the pregnant woman is important because normal reductions in the plasma enzyme levels combined with a genetic variant could prove fatal if exposed to Succinylcholine or a local ester anesthetic like Chloroprocaine.
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Malignancy- Impaired levels of pseudocholinesterase enzyme have been associated with malignant tumors and carcinoma.
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Cardiopulmonary Diseases- Studies suggest a marked reduction in the enzyme pseudocholinesterase activity in patients suffering from cardiopulmonary bypass. The matter worsens if it is associated with a genetic variant.
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Leprosy- Pseudocholinesterase deficiency is found to be seen more commonly associated with individuals suffering from lepromatous leprosy.
What Is the Relevance of Pseudocholinesterase Deficiency to Anesthesia Providers?
Pseudocholinesterase deficiency, whether inherited or acquired, should be considered by providers that administer Succinylcholine, including anesthesia, intensive care unit (ICU), emergency department, and perioperative personnel, including the nurses to the patients. Special screening should be done for pregnant women who have either genetic or acquired variants of the condition. Genetic tests and molecular tests should be done to make informed choices about the patient’s care plan. The anesthetist must also predict what diseases, conditions, or drugs would cause disturbances in a patient’s enzyme activity and make wise choices about the patient’s care based on the available data.
What Drugs to Avoid In Pseudocholinesterase Deficiency?
What Are the Tests for Pseudocholinesterase Deficiency?
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Biochemical Assays: Serum pseudocholinesterase activity determines if there is a quantitative defect in enzyme activity. The normal levels ranged between 3,200 to 6,600 IU/L.
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Molecular Testing Like PCR (Polymerase Chain Reaction): This can be done to determine the qualitative and quantitative variants of the enzyme.
What Is the Treatment of Pseudocholinesterase Deficiency?
There is no known treatment for pseudocholinesterase deficiency. However, there are interventions and precautions that, if taken, can speed up the onset of recovery in an individual exposed to Succinylcholine or Mivacurium. The mainstay of treatment in these patients is to continue mechanical ventilation with sedation and continue peripheral nerve monitoring until paralysis ends and the muscle activity returns to normal.
Administration of whole blood, fresh frozen plasma, packed red blood cells, and human serum cholinesterase is an intervention that can be done to shorten the duration of the block.
The golden rule is to let the individual recover spontaneously. It has been theorized in the literature that the administration of whole blood has successfully reversed prolonged apnea and paralysis after the administration of Succinylcholine in patients with pseudocholinesterase deficiency.
Note: Patients with pseudocholinesterase deficiency should avoid drugs like Succinylcholine and Mivacurium to prevent the future occurrence of prolonged paralysis.
Conclusion
Pseudocholinesterase deficiency is a genetic or inherited condition characterized by prolonged periods of apnea and paralysis following clinical doses of Succinylcholine or Mivacurium. The metabolism of Succinylcholine, Mivacurium, and ester local anesthetics is potentially impaired in these patients. All anesthesia providers should use a peripheral nerve stimulator, including Succinylcholine when using any muscle relaxant. Another effective method to prevent its incidence is to list Mivacurium and Succinylcholine drugs as sources of patient allergies. Reoccurrence can also be reduced by a thoroughly conducted preoperative assessment by the anesthesia and healthcare provider. Patients suffering from Pseudocholinesterase deficiency should also be properly educated about the adverse reactions of these drugs. Lastly, having sound knowledge of this condition's aspects will help the healthcare provider provide accurate information to the patients and their families.
