Clinical outcomes and kinetics of propanil following acute self-poisoning: a prospective case series.

BACKGROUND: Propanil is an important cause of death from acute pesticide poisoning, of which methaemoglobinaemia is an important manifestation. However, there is limited information about the clinical toxicity and kinetics. The objective of this study is to describe the clinical outcomes and kinetics of propanil following acute intentional self-poisoning. METHODS: 431 patients with a history of propanil poisoning were admitted from 2002 until 2007 in a large, multi-centre prospective cohort study in rural hospitals in Sri Lanka. 40 of these patients ingested propanil with at least one other poison and were not considered further. The remaining 391 patients were classified using a simple grading system on the basis of clinical outcomes; methaemoglobinaemia could not be quantified due to limited resources. Blood samples were obtained on admission and a subset of patients provided multiple samples for kinetic analysis of propanil and the metabolite 3,4-dichloroaniline (DCA). RESULTS: There were 42 deaths (median time to death 1.5 days) giving a case fatality of 10.7%. Death occurred despite treatment in the context of cyanosis, sedation, hypotension and severe lactic acidosis consistent with methaemoglobinaemia. Treatment consisted primarily of methylene blue (1 mg/kg for one or two doses), exchange transfusion and supportive care when methaemoglobinaemia was diagnosed clinically. Admission plasma concentrations of propanil and DCA reflected the clinical outcome. The elimination half-life of propanil was 3.2 hours (95% confidence interval 2.6 to 4.1 hours) and the concentration of DCA was generally higher, more persistent and more variable than propanil. CONCLUSION: Propanil is the most lethal herbicide in Sri Lanka after paraquat. Methylene blue was largely prescribed in low doses and administered as intermittent boluses which are expected to be suboptimal given the kinetics of methylene blue, propanil and the DCA metabolite. But in the absence of controlled studies the efficacy of these and other treatments is poorly defined. More research is required into the optimal management of acute propanil poisoning.

Enzyme-based assay for quantification of chlorpyrifos oxon in human plasma.

Chlorpyrifos oxon (CPO) is the active metabolite of the pesticide chlorpyrifos that inhibits cholinesterases at high reaction rates. Chlorpyrifos is of major concern because it causes some ten thousand fatalities each year, mostly due to suicidal attempts. Notwithstanding, toxicokinetic studies on chlorpyrifos in humans are scarce and CPO has not been detected hitherto in human blood. Knowledge of the concentration and the time course of CPO in poisonings would be helpful to better design antidotal strategies, particularly with oximes. Owing to the exceptionally fast covalent binding to butyrylcholinesterase we searched for an enzyme-based assay for CPO determination. We succeeded in a simple procedure where CPO is titrated with purified equine butyrylcholinesterase. The assay requires less than 0.2 mL EDTA plasma and allows the quantification of CPO down to 0.5 nM. CPO is first extracted from plasma with n-pentane, thereby largely excluding the majority of the more hydrophilic pesticide oxons from possible cross-reactions. When chlorpyrifos incorporation is ascertained the assay may be considered largely specific. The new procedure enabled the assessment of the extent of reversible binding of CPO to human albumin, amounting to 85% under physiological conditions. The assay allowed the quantification of CPO in the plasma of a poisoned patient, where the active metabolite was about two orders of magnitude lower than chlorpyrifos. Similar to the parent compound its oxon showed the same tendency to persist for longer periods, thus calling for a change of the usual oxime dosage regimen.