Final Diagnosis -- Organophosphate Insecticide Poisoning

FINAL DIAGNOSIS: ORGANOPHOSPHATE INSECTICIDE POISONING

Case Discussion - Insecticide Poisoning:

Pet Agree^TM is a flea dip which contains chlorpyrifos at a 3.84% concentration mixed with an inert vehicle. The ingestion of this organophosphate insecticide produced symptoms related to impaired degradation of acetylcholine, including pinpoint pupils, sweating, drooling, and, most dramatically, paralysis. Confirmation of the clinically suspected exposure was obtained through the identification of the active ingredient, in a urine sample from the patient, by gas chromatography-mass spectroscopy.

The neuro-physiological deficits observed in patients with organophosphate insecticide poisoning is related to irreversible binding of the organophophate to the enzyme that degrades acetylcholine at nerve endings. In this patient, the earliest measurement of total serum cholinesterase showed activity that was only 0.5% of the lower range of normal activity. The dibucaine number, which is not usually interpreted in cases like this (see the section on cholinesterase, acetylcholinesterase, and dibucaine index), showed much less inhibition than normal, possibly because all of the enzyme that would normally be inhibited had already been irreversibly inhibited by the organophophate insecticide, and because the available activity of the enzyme was already low. By the second day of hospitalization, the cholinesterase activity had begun to increase.

This patient was treated with atropine and pralidoxime. The atropine acted to block the muscarinic effects of increased acetylcholine on the respiratory, gastrointestinal, and cardiovascular systems. The pralidoxime acted to 'regenerate" the damaged acetylcholinesterase. A measure of the success of the pralidoxime is that the red cell acetylcholinesterase activity had returned to normal levels by about 3 1/2 days after the poisoning.

The patient recovered without apparent permanent sequelae. The mild anemia noted is unrelated to the organophosphate; the borderline hyponatremia was probably related to intravenous therapy.

SELECTED READINGS:

1. Bardin PG et al. Organophosphate and carbamate poisoning. Arch Intern Med 1994;154:1433-1441. This readable review paper stresses clinical presentation and management.
2. Burtiss CA and Ashwood ER. Tietz Textbook of Clinical Chemistry. 2nd Edition, Saunders, New York, 1994. This standard clinical chemistry text has discussions of GC-MS (pp. 237-242) and organophosphate insecticide poisoning (pp. 878-879).
3. Dietz AA et al. Colorimetric Determination of Serum Cholinesterase and Its Genetic Variants by the Propionylthiocholine Dithiobis (Nitrobenzoic Acid) Procedure. Clin Chem 1973;19:1309-1313. This paper presents the range of genetic variants and discusses their differential diagnosis using the dibucaine index.
4. Hardman JG et al. Chapter 8. Anticholinesterase Agents, in Goodman and Gilman's The Pharmacologic Basis of Therapeutics. 9th edition, McGraw Hill, New York, 1966, pp. 161-176. This classic pharmacology text provides an excellent overview of the physiology of acetylcholine and the toxicology of organophosphate insecticides.
5. Wilson IB, and Ginsberg S. Reactivation of Acetylcholinesterase Inhibited by Alkylphosphates. Arch Biochem Biophys 1955;54:569-571. This small landmark paper demonstrates that the "irreversible" inhibition of acetylcholinesterase by organophosphate insecticides can in fact be reversed with an appropriately chosen nucleophilic reagent.