Pharmacology, Toxicology, and Therapeutics Department, University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Wellcome Trust Critical Care Laboratory for Large Animals, University of Edinburgh, Edinburgh, UK.
Clin Toxicol (Phila). 2022 Jun;60(6):725-736. doi: 10.1080/15563650.2022.2028803. Epub 2022 Feb 11.
Patients who require mechanical ventilation after self-poisoning with ingested organophosphorus (OP) insecticides often die. Aspiration of stomach contents may contribute to lung injury and lethality. This study was designed to assess the severity of direct and indirect pulmonary injury created by pulmonary instillation of mixtures of OP insecticide, solvent (Solv) and porcine gastric juice (GJ) compared to controls.
Terminally anaesthetised minipigs (groups = 5) were exposed to sham bronchoscopy or given mixtures (0.5 mL/kg) of: saline, GJ, OP insecticide and GJ (OP + GJ), or Solv and GJ (Solv + GJ), placed into the right lung, and monitored for 48 h. Lung injury was assessed through analysis of bronchoalveolar lavage fluid (BALF), computed tomography and histopathology.
OP + GJ created a direct lung injury consisting of neutrophil infiltration, oedema and haemorrhage, as well as indirect injury to the other lung. OP + GJ directly-injured lung parenchyma had increased concentrations of BALF protein, albumin, IL-6, IL-8 and C-reactive protein (CRP) at 24 h ( < 0.05), and BALF protein, albumin and CRP at 48 h ( < 0.05), when compared with controls. Aspiration of GJ produced similar direct effects to OP + GJ but less indirect lung injury. Lung injury was less severe after Solv + GJ, for combined lung histopathology scores (vs. OP + GJ, < 0.05) and for the proportion of directly-injured lung that was poorly/non-aerated at 48 h.
Pulmonary instillation of OP + GJ created more lung damage than controls or Solv + GJ. In patients with severe OP insecticide poisoning and reduced consciousness, early airway protection is likely to reduce pulmonary damage.
因摄入有机磷(OP)杀虫剂而需要机械通气的患者通常会死亡。胃内容物的吸入可能导致肺损伤和致死。本研究旨在评估与对照组相比,通过肺内灌注 OP 杀虫剂、溶剂(Solv)和猪胃(GJ)混合物引起的直接和间接肺损伤的严重程度。
麻醉的小型猪(每组 5 只)接受假支气管镜检查或给予以下混合物(0.5 mL/kg):盐水、GJ、OP 杀虫剂和 GJ(OP+GJ)或 Solv 和 GJ(Solv+GJ),置于右肺,并在 48 小时内进行监测。通过分析支气管肺泡灌洗液(BALF)、计算机断层扫描和组织病理学评估肺损伤。
OP+GJ 造成直接肺损伤,包括中性粒细胞浸润、水肿和出血,以及对另一个肺的间接损伤。OP+GJ 直接损伤的肺实质在 24 小时时 BALF 蛋白、白蛋白、IL-6、IL-8 和 C 反应蛋白(CRP)浓度升高(<0.05),在 48 小时时 BALF 蛋白、白蛋白和 CRP 浓度升高(<0.05),与对照组相比。GJ 的吸入产生了类似于 OP+GJ 的直接作用,但间接肺损伤较小。与 OP+GJ 相比,Solv+GJ 引起的肺损伤较轻,在联合肺组织病理学评分(<0.05)和 48 小时时直接损伤的肺充气不良/非充气的比例较低。
OP+GJ 的肺内灌注引起的肺损伤比对照组或 Solv+GJ 更严重。在严重的 OP 杀虫剂中毒和意识降低的患者中,早期气道保护可能会减少肺损伤。