People deficient in pseudocholinesterase can have prolonged apnea following surgery, due to a failure to metabolize muscle relaxants such as suxamethonium or mivacurium.
There are two related enzymes able to hydrolyze acetylcholine:
(1) acetylcholinesterase (true cholinesterase, or cholinesterase I): found in erythrocytes, lungs, spleen, nerve endings and gray matter of the brain
(2) acylcholine acylhydrolase (pseudocholinesterase, or cholinesterase II): found in liver, pancreas, heart, white matter of the brain, and serum
Decreases in serum pseudocholinesterase activity may occur with:
(1) genetic inheritance
(2) severe liver disease
(3) suxamethonium overdosage.
|
Genetic Phenotypes |
Code |
Alternate |
|
usual |
U |
E U 1 |
|
abnormal or atypical |
A |
E A 1 |
|
fluoride deficiency |
F |
E F 1 |
|
silent type I |
S |
E S 1 |
|
silent type II |
T |
E T 1 |
Dibucaine and fluoride inhibition can be used to identify the type of pseudocholinesterase defect. Two tests are run in parallel - one with dibucaine or fluoride added and the other without. The degree of inhibition caused by the dibucaine or fluoride is compared to the untreated reaction.
percent inhibition = "number" =
= (1 - ((absorbance of inhibited reaction mixture) / (absorbance of uninhibited reaction mixture)) * 100
A more accurate form is to correct for reaction volume change after inhibitor addition:
percent inhibition = "number" =
= (1 - ((absorbance of inhibited reaction mixture) / ((absorbance of uninhibited reaction mixture)* (volume uninhibited reaction) / (volume inhibited reaction)) * 100
From the pattern of enzyme activity, dibucaine inhibition and fluoride inhibition it is possible to infer the phenotype and likely sensitivity to muscle relaxants.
|
Phenotype |
Relative Enzyme Activity |
Dibucaine Number |
Fluoride Number |
Sensitivity to Succinylcholine |
|
UU |
normal (100) |
76-87 |
55-70 |
no |
|
UF |
80 |
70-80 |
45-54 |
+/- |
|
UA |
78 |
51-71 |
42-59 |
+/- |
|
US |
65 |
80 |
64 |
+/- |
|
FS |
61 |
67 |
37 |
moderate |
|
AF |
60 |
39-59 |
27-38 |
moderate |
|
FF |
50 |
63-69 |
30-37 |
moderate |
|
AA |
50 |
8-30 |
10-28 |
very |
|
AS |
20 |
21 |
23 |
very |
|
TT |
3 |
64-72 |
66-70 |
very |
|
ST |
2 |
|
|
very |
|
SS |
0 |
1-9 |
29-41 |
very |
after Table 1.3, page 8, Sawhney(1986)
Limitations:
• Hemolysis can result in false elevations, due to release of actylcholinesterase from within the red blood cells. Moderate hemolysis does not interfere if red blood cell ghosts are removed by centrifugation.
• Enzyme stable for 6 hours at room temperature, 1 week at 4°C, and 6 months at -70°C
• Specimen should not be repeatedly frozen and thawed.
• Specimens from patients with apnea or paralysis should be collected after the paralysis has resolved, since metabolites of the drugs may interfere with assays.
Specialty: Endocrinology, Clinical Laboratory
