title: Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial.
abstract: BACKGROUND
  Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit.
  
  
  RESULTS
  We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit.
  
  
  CONCLUSIONS
  Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.
authors: Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom.
authors: Michael
authors: M
authors: Eddleston
authors: Peter
authors: P
authors: Eyer
authors: Franz
authors: F
authors: Worek
authors: Edmund
authors: E
authors: Juszczak
authors: Nicola
authors: N
authors: Alder
authors: Fahim
authors: F
authors: Mohamed
authors: Lalith
authors: L
authors: Senarathna
authors: Ariyasena
authors: A
authors: Hittarage
authors: Shifa
authors: S
authors: Azher
authors: K
authors: K
authors: Jeganathan
authors: Shaluka
authors: S
authors: Jayamanne
authors: Ludwig
authors: L
authors: von Meyer
authors: Andrew H
authors: AH
authors: Dawson
authors: Mohamed Hussain Rezvi
authors: MH
authors: Sheriff
authors: Nick A
authors: NA
authors: Buckley
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000328:Adult; D000931:Antidotes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001285:Atropine / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007306:Insecticides / Q000506:poisoning*; D007442:Intubation, Intratracheal; D008297:Male; D009944:Organoplatinum Compounds / Q000506:poisoning*; D011041:Poisoning / Q000401:mortality; D011220:Pralidoxime Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000931:Antidotes; D007306:Insecticides; D009944:Organoplatinum Compounds; D011220:Pralidoxime Compounds; D001285:Atropine; D000110:Acetylcholinesterase; C028797:pralidoxime