Part 4: The Cholinergic Toxidrome
Section 10: Laboratory Assessment of the Cholinergic Toxidrome Red Blood Cell (RBC) and Serum Cholinesterase
- Learning Objectives
- The Two Types of Cholinesterase Levels
- Sources of Error in the Measurement of Cholinesterase Levels (Optional Reading)
- Case Example (Optional Reading)
- Variations among Laboratories (Optional Reading)
- Levels Correlated with Toxicity (Optional Reading)
- The Role of Baseline Cholinesterase Levels (Optional Reading)
- Other Causes of Cholinesterase Level Abnormalities
- Key Points
- Progress Check
Course: WB 1098
CE Original Date: October 16, 2007
CE Renewal Date: October 16, 2010
CE Expiration Date: October 16, 2012
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Upon completion of this section, you will be able to:
- Describe the usefulness and limitations of laboratory analysis of RBC and serum cholinesterase levels.
linesterase levels play an important role in the emergency diagnosis and treatment of cholinesterase inhibitor toxicity.
There are two types of cholinesterase levels
- Red Blood Cell (RBC) cholinesterase (also called true cholinesterase).
- Serum cholinesterase (also called pseudocholinesterase or butyrylcholinesterase).
In general, the key differences between RBC cholinesterase and serum cholinesterase are shown in the following table.
|RBC cholinesterase||Serum cholinesterase|
|Duration of depression (Reigart and Roberts 1999)||Several days to a few weeks||1-3 months|
|Onset of depression||Later||Early|
*That is, it is thought to more closely approximate cholinesterase levels in the neurosynapse.
**Although one author contends that there is no evidence that this is the case for nerve agents. (Wiener and Hoffman 2004)
Listed below are some of the sources of error in the measurement and interpretation of cholinesterase levels.
- Normal ranges of RBC and serum cholinesterase vary widely between individuals (and even in the same individual at different times). (Karalliedde 2002; Leikin, Thomas et al. 2002; Wessels, Barr et al. 2003; Wiener and Hoffman 2004)
- Because of this, a person who usually has a “high-normal” level of cholinesterase could be significantly toxic but his or her cholinesterase level could decrease only into the “low-normal” range. (Tareg et al. 2001)
- Thus, the toxic patient would have a falsely normal test result. (Midtling, Barnett et al. 1985; Jamal 1997; Clark 2002) (One author indicates that for serum cholinesterase there is a 300% difference between the lower and upper normal values. (Erdman 2004))
- Thus, unless pre-exposure levels are available for comparison, only a level of inhibition greater than that due to interindividual variability (about 25% for RBC cholinesterase) can be considered significant. (Ray 1998)
- Errors in laboratory results can also occur if samples are stored at room temperature, because cholinesterase bound to un-aged inhibitors can undergo significant spontaneous reactivation. (Ray 1998)
- Another source of error, even with modern testing kits, is lack of experience and skill of the laboratory technician. (Wessels, Barr et al. 2003)
In one study of 29 farm workers who were symptomatic after exposure to pesticides, none had RBC or serum cholinesterase levels below the lower limit of normal. (Midtling, Barnett et al. 1985)
Due to differences in techniques, the absolute cholinesterase values vary from laboratory to laboratory. (Minton and Murray 1988) Laboratories may report their findings as percentages of average or normal (in unexposed subjects) rather than as absolute values.
Even with the more accurate RBC cholinesterase, the point at which various authors have suggested that toxicity begins to appear ranges from 40% to 75% of normal values. (Carlton, Simpson et al. 1998) (Romano, McDonough et al. 2001; Clark 2002)
Some authors suggest that, when compared to an individual’s baseline value, changes in RBC cholinesterase levels correlate well with cholinesterase inhibitor toxicity. (Tareg et al. 2001; Clark 2002) However, such baseline values are rarely available except, perhaps, in occupational settings where workers are monitored for ongoing exposures.
Other conditions, besides exposure to cholinesterase inhibitors can cause abnormalities in cholinesterase levels.
|RBC cholinesterase||Serum cholinesterase|
- RBC and serum (uninhibited) cholinesterase levels are used to approximate levels in neural tissue, since the latter are impractical to obtain.
- These tests are rarely available in time to guide the emergency treatment decisions. Initial emergency management should therefore be based on clinical assessment.
- When available, test results must be interpreted with caution, because of
- Interindividual and intraindividual differences in normal cholinesterase levels.
- Other medical conditions and substances that can alter cholinesterase levels.
- Laboratory errors.