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

Roberts DM, Heilmair R, Buckley NA, Dawson AH, Fahim M, Eddleston M, Eyer P - BMC Clin Pharmacol (2009)

Bottom Line: Admission plasma concentrations of propanil and DCA reflected the clinical outcome.Propanil is the most lethal herbicide in Sri Lanka after paraquat.More research is required into the optimal management of acute propanil poisoning.

View Article: PubMed Central - HTML - PubMed

Affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. 1darren1@gmail.com

ABSTRACT

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.

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The ratio of propanil:DCA concentration relative to time.
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Figure 5: The ratio of propanil:DCA concentration relative to time.

Mentions: Both propanil and DCA were quantified in 300 samples allowing for temporal changes in the ratio of propanil:DCA to be determined as shown in figure 5. It is observed that prior to 10 hours post-ingestion the ratio varies widely, which is probably due to ongoing propanil absorption and bioconversion to DCA. After 10 hours, however, the ratio is consistently less than 1.0 meaning that the concentration of DCA is higher than propanil. This could be due to propanil having higher clearance or a larger volume of distribution (Vd) than DCA. However, the observed half-life of DCA may also be strongly influenced by the rate of formation from propanil (a type of 'flip-flop' kinetics[22]).


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

Roberts DM, Heilmair R, Buckley NA, Dawson AH, Fahim M, Eddleston M, Eyer P - BMC Clin Pharmacol (2009)

The ratio of propanil:DCA concentration relative to time.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2656468&req=5

Figure 5: The ratio of propanil:DCA concentration relative to time.
Mentions: Both propanil and DCA were quantified in 300 samples allowing for temporal changes in the ratio of propanil:DCA to be determined as shown in figure 5. It is observed that prior to 10 hours post-ingestion the ratio varies widely, which is probably due to ongoing propanil absorption and bioconversion to DCA. After 10 hours, however, the ratio is consistently less than 1.0 meaning that the concentration of DCA is higher than propanil. This could be due to propanil having higher clearance or a larger volume of distribution (Vd) than DCA. However, the observed half-life of DCA may also be strongly influenced by the rate of formation from propanil (a type of 'flip-flop' kinetics[22]).

Bottom Line: Admission plasma concentrations of propanil and DCA reflected the clinical outcome.Propanil is the most lethal herbicide in Sri Lanka after paraquat.More research is required into the optimal management of acute propanil poisoning.

View Article: PubMed Central - HTML - PubMed

Affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. 1darren1@gmail.com

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus