title: Clinical outcomes and kinetics of propanil following acute self-poisoning: a prospective case series.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. 1darren1@gmail.com
authors.forename: Darren M
authors.initials: DM
authors.lastname: Roberts
authors.forename: Renate
authors.initials: R
authors.lastname: Heilmair
authors.forename: Nick A
authors.initials: NA
authors.lastname: Buckley
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Dawson
authors.forename: Mohamed
authors.initials: M
authors.lastname: Fahim
authors.forename: Michael
authors.initials: M
authors.lastname: Eddleston
authors.forename: Peter
authors.initials: P
authors.lastname: Eyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000814:Aniline Compounds / Q000097:blood; D005078:Exchange Transfusion, Whole Blood; D005260:Female; D006540:Herbicides / Q000493:pharmacokinetics* / Q000506:poisoning*; D006801:Humans; D008297:Male; D008708:Methemoglobinemia / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D008751:Methylene Blue / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D011041:Poisoning / Q000401:mortality / Q000628:therapy*; D011411:Propanil / Q000493:pharmacokinetics* / Q000506:poisoning*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D013188:Sri Lanka; D013405:Suicide; D013406:Suicide, Attempted; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000814:Aniline Compounds; D006540:Herbicides; C014464:3,4-dichloroaniline; D011411:Propanil; D008751:Methylene Blue