The Testing Process

When evaluating AChE tests clinically, three factors must be kept in mind:

1. Anticholinesterase agents depress AChE levels.

2. Baseline levels may vary 23% among individuals.

3. The testing results can be affected by extraneous health problems, medications, and illegal drugs.

It is common for consultants to encounter patients who have been diagnosed with pesticide poisoning and removed from duty for extended periods of time as a result of elevated AChE levels. It must be kept in mind that organophosphates and carbamates depress AChE activity levels, and the tests measure an enzyme activity and not the concentration of a chemical (5,6).

Any monitoring program that does not take into consideration the genetic variation in AChE levels is invalid. Because of the 23% variation, there is a wide range of "normal." If AChE levels are determined only after an alleged exposure, the possibility of low but normal AChE activity levels could lead to a false-positive finding.

Acetylcholinesterase activity levels are affected by illness, medications, and illegal drugs. Hepatorenal and neuromuscular diseases, wasting, and alcoholism can affect the levels by altering AChE metabolism. Medications, especially those affecting the neuromuscular junction such as physostigmine and Aricept, can alter the activity levels; cocaine can alter levels (5).

There are two modes in which AChE testing is utilized: preexposure testing and monitoring and exposure testing.

Preexposure Testing

Beginning in 1974, California has required the testing of pesticide applicators, mixer-loaders, flagmen, maintenance personnel, supervisors, and others who come in daily contact with class I or II OPs and CMs. The program includes criteria for testing, testing protocols, and actions to be taken given various levels of AChE activity depression. These are summarized in Table 9.1 (7-9).

Table 9.1. The California cholinesterase monitoring protocol baseline. Indication: if an employee is handling class I or II organophosphate or carbamate pesticides more than 6 days in a 30-day period. Testing: average of two tests not closer than 3 days and not further apart than 15 days from each other. If the tests are not within 15% of each other, a third test is performed and the two closest to each other are averaged. Periodic testing

Timing: if spraying 6 days in a 30-day period Three tests at 30-day intervals Then testing at 60-day intervals

More often as determined by the medical supervisor if the values are inconsistent or low or if the employee has been involved in an exposure.

Action: plasma or RBC activity levels falls to 80% of baseline: report to employer advising an investigation into the work practices of the handler.

Plasma falls to 60% of baseline or RBC falls to 70% of baseline: remove employee from exposure.

Employee must remain away from exposure but may work at another job task not requiring exposure until both the serum and RBC cholinesterase activity levels return to 80% of baseline.

Source: Adapted from the California Environmental Protection Agency guidelines (7).

Participants in the program include:

1. Employers who select the employees who need to be tested and send them to the clinic

2. Employees who are tested and often miss their appointments

3. Physicians who interpret the tests and send the results and recommendations to the employer

4. County agricultural officials who monitor the employers for compliance

5. State researchers who monitor the program for effectiveness

Surveys have demonstrated that most monitoring is done incorrectly. Ames and Associates (7) have found four categories of problems with AChE monitoring:

1. Employers fail to refer employees for baseline measurements and monitoring.

2. Laboratories use the wrong methods or fail to conduct the tests appropriately.

3. Physicians fail to interpret test results properly and to make the appropriate recommendations.

4. There are insufficient numbers of county employees to monitor the employers effectively.

5. The state is unable to monitor physicians because training and certification is not required.

Proposed solutions include employer and physicians training, physician training, and the standardization of laboratory kits and procedures (7).

Exposure Testing

Acetylcholinesterase testing is beneficial only for carbamate and organophos-phate poisoning, and these agents comprise the minority of compounds used as pesticides. He and Associates (10), writing in China, found the problem of incorrect diagnosis of carbamate and organophosphate poisoning based on low but normal AChE levels measured in cholinesterase testing. Several patients died as a result of injudicious use of atropine (a cholinergic antagonist) as treatment for poisoning with pyrethroids, which have no effect on AChE levels.

Currently two testing procedures are used to document carbamate or organophosphate exposure and recovery: testing for exposure with ongoing monitoring and testing without ongoing monitoring (5,11).

Ongoing Monitoring

A dip in AChE activity levels is expected in a person who is subject to ongoing monitoring and who has been exposed to carbamate or organophosphate pesticides. Because the patient may not be symptomatic, the decrease in AChE monitoring levels may be the only finding. A dip of greater than 20% is considered evidence of overexposure.

Without Monitoring

Workers might be exposed to a substantial amount of an organophosphate or carbamate and have immediate signs and symptoms of poisoning. Depression of AChE values can be variable and might not correspond to the severity of the clinical findings. The decision to treat should be based on clinical, not laboratory, considerations (5,11).

In Japan more than 600 persons were treated for sarin poisoning caused by terrorists. The decision to treat was based on clinical findings. Acetylcholinesterase testing was useful in follow-up of the exposed persons, and it took up to 3 months before levels stabilized at presumably normal levels (12).

In patients with documented carbamate or organophosphate poisoning and with depressed or normal AChE levels, overexposure can be reflected in a 20% increase after the exposure, representing recovery of the activity levels. Plasma levels can be expected to increase first, followed by the RBC levels (1).

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