Organophosphate pesticide poisoning: benefits and limitations of oxime therapy

INTRODUCTION: Organophosphate pesticide poisoning remains a major global health problem, accounting for more than 100,000 deaths annually. For decades, the use of oximes in treating the manifestations of organophosphate poisoning has been controversial. We report two cases of organophosphate poisoning caused by monocrotophos and parathion that clearly illustrate both the benefits and the limitations of oxime therapy. These cases highlight the importance of the assessment of acetylcholinesterase activity for identifying patients that benefit from oxime treatment. METHODS: We characterized two cases of organophosphate poisoning using spectrophotometric measurements of acetylcholinesterase and butyrylcholinesterase activity, the reactivatability of patients' acetylcholinesterase, and the inhibitory potential of patients' plasma. Gas chromatography-electron ionization mass spectrometry was used to identify the respective pesticides. In addition, liquid chromatography-electrospray ionization-tandem mass spectrometry was used to quantify atropine plasma concentrations and obidoxime plasma concentrations were determined by liquid chromatography coupled with diode-array detection. CASE REPORTS: The two distinct cases of organophosphate poisoning demonstrate that an early determination of acetylcholinesterase activity, when interpreted alongside the clinical course, can guide clinical decision-making regarding oxime therapy. In the presence of completely aged acetylcholinesterase, as observed in case 1 (monocrotophos), oxime treatment is unlikely to be beneficial. In contrast, in case 2 (parathion), oxime therapy appears to be an effective therapeutic option. DISCUSSION: Large clinical trials demonstrating a clinically relevant benefit of obidoxime and pralidoxime therapy in organophosphate poisoning are not available. Nevertheless, the present study shows that inexpensive and easy to perform spectrophotometric assessment of patient acetylcholinesterase activity and reactivatability is crucial for avoiding unnecessary oxime treatment and for clearly identifying patients who would benefit from this therapy. CONCLUSION: Laboratory parameter-guided management of organophosphate poisoning, based on acetylcholinesterase activity, acetylcholinesterase reactivatability, and plasma inhibitory activity, supports clinical decision-making regarding oxime therapy.