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Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial
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 whethe...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696321/ https://www.ncbi.nlm.nih.gov/pubmed/19564902 http://dx.doi.org/10.1371/journal.pmed.1000104 |
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author | Eddleston, Michael Eyer, Peter Worek, Franz Juszczak, Edmund Alder, Nicola Mohamed, Fahim Senarathna, Lalith Hittarage, Ariyasena Azher, Shifa Jeganathan, K. Jayamanne, Shaluka von Meyer, Ludwig Dawson, Andrew H. Sheriff, Mohamed Hussain Rezvi Buckley, Nick A. |
author_facet | Eddleston, Michael Eyer, Peter Worek, Franz Juszczak, Edmund Alder, Nicola Mohamed, Fahim Senarathna, Lalith Hittarage, Ariyasena Azher, Shifa Jeganathan, K. Jayamanne, Shaluka von Meyer, Ludwig Dawson, Andrew H. Sheriff, Mohamed Hussain Rezvi Buckley, Nick A. |
author_sort | Eddleston, Michael |
collection | PubMed |
description | 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. METHODS AND FINDINGS: 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. TRIAL REGISTRATION: Controlled-trials.com ISRCTN55264358 Please see later in the article for Editors' Summary |
format | Text |
id | pubmed-2696321 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26963212009-06-30 Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial Eddleston, Michael Eyer, Peter Worek, Franz Juszczak, Edmund Alder, Nicola Mohamed, Fahim Senarathna, Lalith Hittarage, Ariyasena Azher, Shifa Jeganathan, K. Jayamanne, Shaluka von Meyer, Ludwig Dawson, Andrew H. Sheriff, Mohamed Hussain Rezvi Buckley, Nick A. PLoS Med Research Article 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. METHODS AND FINDINGS: 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. TRIAL REGISTRATION: Controlled-trials.com ISRCTN55264358 Please see later in the article for Editors' Summary Public Library of Science 2009-06-30 /pmc/articles/PMC2696321/ /pubmed/19564902 http://dx.doi.org/10.1371/journal.pmed.1000104 Text en Eddleston et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Eddleston, Michael Eyer, Peter Worek, Franz Juszczak, Edmund Alder, Nicola Mohamed, Fahim Senarathna, Lalith Hittarage, Ariyasena Azher, Shifa Jeganathan, K. Jayamanne, Shaluka von Meyer, Ludwig Dawson, Andrew H. Sheriff, Mohamed Hussain Rezvi Buckley, Nick A. Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial |
title | Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial |
title_full | Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial |
title_fullStr | Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial |
title_full_unstemmed | Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial |
title_short | Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial |
title_sort | pralidoxime in acute organophosphorus insecticide poisoning—a randomised controlled trial |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696321/ https://www.ncbi.nlm.nih.gov/pubmed/19564902 http://dx.doi.org/10.1371/journal.pmed.1000104 |
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