Poisoning with the S-Alkyl organophosphorus insecticides profenofos and prothiofos

Eddleston, Michael, Franz Worek, Peter Eyer, Horst Thiermann, L. Von Meyer, K. Jeganathan, M. H. R. Sheriff, A. H. Dawson, and Nicholas A. Buckley. "Poisoning with the S-Alkyl organophosphorus insecticides profenofos and prothiofos." QJM 102, no. 11 (2009): 785-792.

abstract:

Background: Many organophosphorus (OP) insecticides have either two O-methyl or two O-ethyl groups attached to the phosphorus atom. This chemical structure affects their responsiveness to oxime-induced acetylcholinesterase (AChE) reactivation after poisoning. However, several OP insecticides are atypical and do not have these structures.

Aim: We aimed to describe the clinical course and responsiveness to therapy of people poisoned with two S-alkyl OP insecticides—profenofos and prothiofos.

Design: We set up a prospective cohort of patients with acute profenofos or prothiofos self-poisoning admitted to acute medical wards in two Sri Lankan district hospitals. Clinical observation was carried out throughout their inpatient stay; blood samples were taken in a subgroup for assay of cholinesterases and insecticide.

Results: Ninety-five patients poisoned with profenofos and 12 with prothiofos were recruited over 5 years. Median time to admission was 4 (IQR 3–7) h. Eleven patients poisoned with profenofos died (11/95; 11.6%, 95% CI 5.9–20); one prothiofos patient died (1/12; 8.3%, 95% CI 0.2–38). Thirteen patients poisoned with profenofos required intubation for respiratory failure (13/95; 13.7%, 95% CI 7.5–22); two prothiofos-poisoned patients required intubation. Both intubations and death occurred late compared with other OP insecticides. Prolonged ventilation was needed in those who survived—a median of 310 (IQR 154–349) h. Unexpectedly, red cell AChE activity on admission did not correlate with clinical severity—all patients had severe AChE inhibition (about 1% of normal) but most had only mild cholinergic features, were conscious, and did not require ventilatory support.

Conclusions: Compared with other commonly used OP insecticides, profenofos and prothiofos are of moderately severe toxicity, causing relatively delayed respiratory failure and death. There was no apparent response to oxime therapy. The lack of correlation between red cell AChE activity and clinical features suggests that this parameter may not always be a useful marker of synaptic AChE activity and severity after OP pesticide poisoning.

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