Organophosphate Poisoning At a Glance
Organophosphate poisoning is the result of acute or chronic exposure to one of more than forty organophosphate insecticides currently in use. Organophosphates inhibit cholinesterase enzymes, including red blood cell (RBC) cholinesterase and plasma cholinesterase, thereby preventing the breakdown of acetylcholine. Excessive acetylcholine accumulation initially produces stimulatory and subsequently inhibitory effects on neurotransmission.
The diagnosis of organophosphate poisoning is strongly aided by establishing a history of exposure to an insecticide or pesticide. Signs and symptoms of acute organophosphate poisoning are typically seen within 12-24 hours but may manifest within minutes to a few hours of exposure. All signs and symptoms are cholinergic in nature. Commonly reported early symptoms include headache, nausea, dizziness, and hypersecretion (i.e., sweating, salivation, lacrimation, rhinorrhea, bronchorrhea); symptoms of a worsening state include muscle fasciculations, weakness, tremor, vomiting, abdominal cramps, and diarrhea. A wide range of other symptoms may also be noted, including incontinence, defecation, tachycardia, bradycardia, hypertension, cramping of skeletal muscles, bronchospasm, and pulmonary edema. Miosis is commonly observed, as are symptoms of central nervous system (CNS) toxicity, such as anxiety and restlessness.
Pediatric patients often present with a slightly different clinical picture. Seizures and mental status changes (e.g., lethargy, coma) are more commonly observed, along with flaccid muscle weakness, miosis, and excessive salivation. Conversely, bradycardia, muscular fasciculations, lacrimation, and sweating are less common than in adult patients.
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Overall, the exact group of symptoms that present will strongly depend on the type of organophosphate, dose received, route and rate of absorption, and other individual factors. The duration of symptoms depends on the severity of poisoning, the type of organophosphate, and the therapeutic interventions. If organophosphate poisoning is probable, the patient should be treated immediately without waiting for laboratory confirmation.
What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
In general, intact organophosphates cannot be detected in the blood due to rapid hydrolysis by the liver. Therefore, the most commonly used test to confirm acute organophosphate poisoning is measurement of plasma cholinesterase activity. Plasma cholinesterase levels usually decline to less than 50% of the normal value before any symptoms of poisoning are observed. As a rough guide, plasma cholinesterase levels of 20-50% of the normal value are found with mild poisoning, 10-20% with moderate poisoning, and less than 10% in cases of severe toxicity.
A follow-up test that evaluates RBC cholinesterase levels may also be useful in certain circumstances. For example, plasma cholinesterase activity may be decreased by a number of conditions besides organophosphate poisoning. In contrast, depression of RBC cholinesterase activity is more specific for organophosphate poisoning. If both plasma and RBC cholinesterase activities are significantly decreased, the clinical symptoms may be attributed to organophosphate poisoning. (Table 1)
It is important to note, however, that some organophosphates selectively inhibit plasma cholinesterase and, therefore, would yield normal RBC cholinesterase results. Measurement of RBC cholinesterase levels may also be useful when organophosphate poisoning is suspected but plasma cholinesterase levels remain normal. Certain organophosphates selectively inhibit RBC cholinesterase, and observation of a decrease in RBC cholinesterase activity is critical to confirm poisoning by such insecticides.
Because organophosphate metabolites, such as alkylphosphates and phenols, are excreted by the kidneys, urinalysis may aid in identifying and quantifying the parent compound. Typically, metabolites can be detected up to 48 hours after exposure and can demonstrate organophosphate absorption at lower dosages than is required to produce symptoms or to depress cholinesterase activities. For this reason, urinalysis may also be useful in confirming low-dosage chronic exposure to this group of chemicals.
Table 1
| Plasma cholinesterase | RBC cholinesterase |
|---|---|
| < 3 U/mL | < 8 U/mL |
Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?
Several preanalytical variables may affect laboratory results. In the presence of organophosphate or pralidoxime, the inhibition or reactivation of cholinesterase in blood may continue after sample collection. Therefore, the appropriate sampling and storage of blood is crucial to obtaining accurate test results.
Reference ranges for cholinesterase results are method dependent and different for plasma versus RBC cholinesterase. The reference range for RBC cholinesterase depends on the method of normalization of RBC cholinesterase activity: reported values may refer to hematocrit, hemoglobin, erythrocyte volume, or whole blood volume. The reference range for plasma cholinesterase is lower for women than for men, and lower for infants than adults. The use of an incorrect reference range may lead to misinterpretation of an abnormal result as being normal or vice versa.
The normal range of plasma and RBC cholinesterase activities is wide, and day-to-day variations may be as large as 10-20%, making test result interpretation difficult. For example, a plasma cholinesterase activity considered normal based on a population-based reference range might actually be abnormally low for a particular patient. To alleviate this problem, baseline measurements prior to organophosphate exposure should be made for all persons with a high risk of organophosphate exposure (e.g., workers in agriculture and in organic chemical industries).
Despite suspicion of organophosphate poisoning, plasma cholinesterase levels may appear normal in several instances. The elevated activities observed in some obese and diabetic patients, for example, may balance the decreased levels that would arise because of organophosphate poisoning, resulting in normal plasma cholinesterase levels. Certain organophosphates selectively inhibit RBC cholinesterase, and, in these instances, the plasma cholinesterase activity would also be normal. It should be noted that the opposite may also occur: certain organophosphates that selectively inhibit plasma cholinesterase yield normal RBC cholinesterase values.
Decreased plasma cholinesterase activity is not unique to organophosphate poisoning. It may also present in certain types of liver disease, malnutrition, chronic alcoholism, dermatomyositis, and congestive heart failure. Pregnancy, oral contraceptives, and metoclopramide may also cause depression of plasma cholinesterase activity. A number of exogenous substances may reduce plasma cholinesterase activity, including cocaine, carbon disulfide, benzalkonium salts, organic mercury compounds, ciguatoxins, and solanines. In addition, 3% of the healthy population has atypical genetic variants of the enzyme and, as a result, show low normal activities in plasma cholinesterase tests.
Although a depression of RBC cholinesterase activity is more specific for organophosphate poisoning, decreases in RBC cholinesterase activity may be seen in patients receiving antimalarial therapy or in patients with pernicious anemia, paroxysmal nocturnal hemoglobinuria, or certain other rare conditions that damage the RBC membrane. Establishing a history of exposure to an insecticide or pesticide along with a thorough clinical evaluation can aid in ruling out causes unrelated to organophosphate poisoning.
The most common complicating factor in the urinalysis of organophosphate metabolites is the dietary ingestion of low levels of organophosphates.
What Lab Results Are Absolutely Confirmatory for Organophosphate Poisoning?
Currently, there are no laboratory results that are absolutely confirmatory for organophosphate poisoning. Diagnosis must be based on a combination of patient history, signs and symptoms, depressed plasma and/or RBC cholinesterase activity, and response to therapy.
What Factors, If Any, Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?
Pharmacologic treatment of organophosphate poisoning aims to resolve the initial cholinergic crisis and includes administration of atropine and pralidoxime. Atropine is a competitive antagonist of acetylcholine and blocks the muscarinic actions of the latter. As it is able to cross the blood-brain barrier, it may also treat the CNS toxicity of organophosphates. Pralidoxime binds to the catalytic site of cholinesterase where it attacks and removes the phosphate moiety of the inactivated enzyme. Pralidoxime is most effective if administered early (24-48 hours) after exposure. Although pralidoxime should be administered in all cases of known or suspected organophosphate poisoning, it may be ineffective for treating the effects of ciodrin, dimefox, dimethoate, methyldiazinon, methyl-phencapton, phorate, schradan, and Wepsyn.
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