title: Translational toxicological research: investigating and preventing acute lung injury in organophosphorus insecticide poisoning.
abstract: Poisoning through ingestion of organophosphorus (OP) insecticide is a leading cause of suicide globally. Severe poisoning with OP compounds creates an unconscious, paralysed patient with respiratory failure. These symptoms make pulmonary aspiration of stomach contents highly likely, potentially causing an acute lung injury. To explore this hypothesis, we created a Gottingen minipig pulmonary aspiration model (n=26) to investigate the mechanism and severity of lung injury created through pulmonary instillation of 0.5 mL/kg mixtures of porcine gastric juice (GJ), OP and/or its solvent. Early results show that aspiration of OP and GJ causes pulmonary neutrophil sequestration, alveolar haemorrhage and interstitial oedema, with disruption of the alveolar-capillary membrane. Further measurements will include quantitative CT imaging, histopathology scoring, acute lung injury biomarkers and respiratory function. In order to test the validity of the minipig model, a pilot study in Sri Lanka has been devised to observe signs of lung injury in human patients who have ingested OP insecticide with or without clinical evidence of pulmonary aspiration. Lung injury will be assessed with PaO2/FIO2 ratios and physiological dead space measurement. Blood, bronchoalveolar lavage and urine will be taken at 24 and 48 h after poisoning and at 3-4 h in surgical control patients to measure acute lung injury biomarkers. An unpublished toxicology study from Sri Lanka, 2011-2012, showed that over 40% of unconscious poisoned patients with a GCS <9 were not intubated for ambulance transfer between rural and district hospitals. Delay in intubation leads to aspiration pneumonitis and pneumonia in 38%-45% of unconscious poisoned patients. We hypothesise that non-drug assisted placement of supraglottic airways may be a good tool for use in unconscious poisoned patients requiring transfer from small rural hospitals in Asia. They could confer better airway protection than no airway intervention and reduce both morbidity and mortality.
authors.affiliation: Pharmacology, Toxicology and Therapeutics, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Elspeth J
authors.initials: EJ
authors.lastname: Hulse
authors.affiliation: Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Clutton
authors.affiliation: Senior lecturer, School of Clinical Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: G
authors.initials: G
authors.lastname: Drummond
authors.affiliation: Pharmacology, Toxicology and Therapeutics, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: M
authors.initials: M
authors.lastname: Eddleston
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D001999:Bronchoscopy; D004195:Disease Models, Animal; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D062025:Organophosphate Poisoning; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000633:toxicity*; D010100:Oxygen / Q000032:analysis; D053120:Respiratory Aspiration; D013552:Swine; D013556:Swine, Miniature; D057170:Translational Research, Biomedical
chemical_list: D007306:Insecticides; D009943:Organophosphorus Compounds; D010100:Oxygen
keywords: Toxicology