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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.

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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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Non-sustained reversal of methaemoglobinaemia by methylene blue (MB) in a patient with acute propanil poisoning despite multiple bolus doses. The influence of ascorbic acid (Vit C) is not able to be determined from this data in the absence of kinetic data for DCA. (Adapted from Yamashita et al.[3]).
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Figure 9: Non-sustained reversal of methaemoglobinaemia by methylene blue (MB) in a patient with acute propanil poisoning despite multiple bolus doses. The influence of ascorbic acid (Vit C) is not able to be determined from this data in the absence of kinetic data for DCA. (Adapted from Yamashita et al.[3]).

Mentions: Until more data are available it seems reasonable to focus treatment on reversal of methaemoglobinaemia. Because the plasma concentration of DCA remains elevated methaemoglobinaemia will persist for a similar time. [3-5] Methylene blue has a half-life of 5 hours [34] which is shorter than that of DCA in many patients, figures 4 and 6. Rebound poisoning is therefore likely in severe cases from a bolus regimen (see figure 9 for example). This problem can be countered by administration of methylene blue as a constant infusion. This strategy has been reported as successful in dapsone poisoning [35-37] which similarly produces prolonged methaemoglobinaemia and has a much longer half-life than methylene blue.[38,39]


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)

Non-sustained reversal of methaemoglobinaemia by methylene blue (MB) in a patient with acute propanil poisoning despite multiple bolus doses. The influence of ascorbic acid (Vit C) is not able to be determined from this data in the absence of kinetic data for DCA. (Adapted from Yamashita et al.[3]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: Non-sustained reversal of methaemoglobinaemia by methylene blue (MB) in a patient with acute propanil poisoning despite multiple bolus doses. The influence of ascorbic acid (Vit C) is not able to be determined from this data in the absence of kinetic data for DCA. (Adapted from Yamashita et al.[3]).
Mentions: Until more data are available it seems reasonable to focus treatment on reversal of methaemoglobinaemia. Because the plasma concentration of DCA remains elevated methaemoglobinaemia will persist for a similar time. [3-5] Methylene blue has a half-life of 5 hours [34] which is shorter than that of DCA in many patients, figures 4 and 6. Rebound poisoning is therefore likely in severe cases from a bolus regimen (see figure 9 for example). This problem can be countered by administration of methylene blue as a constant infusion. This strategy has been reported as successful in dapsone poisoning [35-37] which similarly produces prolonged methaemoglobinaemia and has a much longer half-life than methylene blue.[38,39]

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