Acute Disease ; Adult ; Humans ; Male ; Occupational Diseases ; Phosgene ; poisoning

Accidents, Occupational ; Adult ; Female ; Humans ; Male ; Phosgene ; analogs & derivatives ; poisoning

Adult ; Female ; Humans ; Male ; Medical Staff ; Middle Aged ; Occupational Exposure ; Phosgene ; poisoning ; Poisoning ; etiology ; Young Adult

Acute Disease ; Adult ; Emergency Nursing ; Emergency Treatment ; Humans ; Male ; Middle Aged ; Phosgene ; analogs & derivatives ; poisoning

Acute Disease ; Humans ; Male ; Middle Aged ; Occupational Diseases ; diagnosis ; therapy ; Phosgene ; poisoning ; Poisoning ; diagnosis ; therapy

Adult ; Chlorine ; poisoning ; Humans ; Male ; Middle Aged ; Phosgene ; poisoning ; Respiratory Distress Syndrome, Adult ; chemically induced

Phosgene is not only a dangerous asphyxiating chemical warfare agent, but also an important chemical raw material, which is widely used in chemical production. According to statistics, there are more than 1 000 phosgene production enterprises in China, with an annual production volume of more than 3 million tons and hundreds of thousands of employees. Therefore, once the leakage accident occurs during production, storage and transportation, it often causes a large number of casualties. In the past 20 years, phosgene poisoning accidents in China have occurred from time to time, and due to the weak irritation, high density, and high concentration of phosgene at the scene of the accident, it often results in acute high-concentration inhalation of the exposed, triggering acute lung injury (ALI), and is very likely to progress to acute respiratory distress syndrome (ARDS), with a mortality rate up to 40%-50%. In view of the characteristics of sudden, mass, concealed, rapid and highly fatal phosgene, and the mechanism of its toxicity and pathogenicity is still not clear, there is no effective treatment and standardized guidance for the sudden group phosgene poisoning. In order to improve the efficiency of clinical treatment and reduce the mortality, this paper has summarized the pathophysiological mechanism of phosgene poisoning, clinical manifestations, on-site treatment, research progress, and innovative clinical therapies by combining the extensive basic research on phosgene over the years with the abundant experience in the on-site treatment of sudden mass phosgene poisoning. This consensus aims to provide guidance for the clinical rescue and treatment of patients with sudden mass phosgene poisoning, and to improve the level of treatment.
Humans ; Phosgene ; Chemical Warfare Agents ; Acute Lung Injury/drug therapy* ; Respiratory Distress Syndrome/therapy* ; Treatment Outcome

OBJECTIVETo observe the protective mechanism of ulinastatin on mice with acute lung injury induced by exposure to phosgene and its relationship to the expressions of matrix metalloproteinase-9 (MMP-9) in the lung tissues.

METHODSSixty-four healthy male SD rats were randomly divided into two groups: the experimental group and the control group. 32 rats in the experiment group were randomly subdivided into four groups: rats with phosgene exposure group, rats with phosgene exposure after saline injected group, rats with phosgene exposure after dexamethasone injected group. 32 rats in the control group were randomly subdivided into four groups: rats with air exposure group, pretreated with ulinastatin before air exposure group, pretreated with saline before air exposure group, pretreated with dexamethasone before air exposure group, 8 animals in each group. After pretreated with the same dose of ulinastatin, saline, dexamethasone respectively, 32 rats in the control groups were exposed to the air on the same condition respectively for 5 min. While after pretreated with the same dose of ulinastatin, saline, dexamethasone respectively, 32 rats in the experiment groups were exposed to the phosgene which the concentration was 8.33 mg/L and with 100% purity for 5 min. The lung wet/dry (W/D) weight ratio was calculated, and total protein content and BALF leukocyte count were detected. The immunohistochemistry was used to detect lung tissue protein expression MMP-9 while enzyme-linked immunosorbent method was employed to detect MMP-9 in serum levels and enzyme original gelatinases spectrum method to detect BALF MMP-9 enzyme original content.

RESULTSCompared with A1, A2, A3, A4 group, the lung W/D, BALF of protein content and WBC count in B1 and B2 group rats were significantly increased, and the difference was statistically significant (P < 0.01). There was statistically significant difference in lung W/D, BALF of protein content and white blood cell count between B1,B2 group and the B3 and B4 rats (P < 0.01). Histological experimental results showed marked hyperemia of alveolar walls, thickening in the lungs, alveolar walls and stroma cells infiltrating and more visible alveolar structure damage in B1 and B2 rats while the alveolar structure, the alveolar walls were clear and slightly thickened with inflammatory cells in B3 and B4 rats. Immunohistochemical result showed that the individual rats, lung and bronchus organization MMP-9 protein were weakly positive, B1 and B2 group MMP-9 protein expression was strongly positive,B3 group and the group MMP B4 lung tissue protein expression-9 weakens, restored to the normal lung tissue of weakly positive expression level. ELISA and gelatinases spectrum testing showed B1 and B2 rats, serum MMP-9 enzyme activity and content increased compared with A1, A2, A3, A4 group, the differences were statistically significant (P < 0.01), and B1, B2 group compared with the B3 and serum B4 group MMP-9 enzyme activity and the differences were obviously decreased, with statistically significant difference (P < 0.01).

CONCLUSIONSUlinastatin has protective effect on phosgene-induced ALL Ulinastatin can inhibit the up-regulation of expression of MMP-9.

Acute Lung Injury ; drug therapy ; etiology ; metabolism ; Animals ; Glycoproteins ; therapeutic use ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Phosgene ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the relationship between the indicators of lung injury and the ratio of angiopoietin-2 (ang-2) to angiopoietin-1 (ang-1) in serum of rats with acute lung injury induced by phosgene.

METHODSEighty four adult male SD rats were randomly divided into 13 phosgene groups and 1 control group. Control group was exposed to fresh air for 5 minutes; the phosgene groups were exposed to phosgene (100% purity of 8.33 mg/L phosgene ) for 5 minutes. At different time points after exposure, the wet/dry weight ratio of mouse lungs was examined, the levels of ang-1 and ang-2 in serum of rats were detected with ELISA assay, and the white blood cell count and total protein levels in bronchoalveolar lavage fluid (BALF) of rats were measured.

RESULTSIn 48 h after exposure,the serum ang-2, lung wet/dry weight ratio, BALF white blood cell count, protein concentration tended to increase with time, and the serum ang-1 tended to decrease with time. The ratios of ang-2 to ang-1 at 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 and 48 h after exposure in phosgene groups were significantly higher than that in control group (P < 0.05 or P < 0.01). There were the positive correlations between ang-2 and lung wet/dry ratio, BALF white blood cell count or protein concentration (P < 0.01). There were the negative correlations between ang-1 and lung wet/dry ratio or BALF white blood cell count (P < 0.01). There were the positive correlations between the ratio of ang-2 to ang-1 and lung wet/dry ratio, BALF white blood cell count or protein concentration (P < 0.01).

CONCLUSIONAfter exposure of rats to phosgene, there is a positive correlation between the ratio of ang-2 to ang-1 and lung injury indicators, which may be an early indicator of the severity of phosgene-induced acute lung injury.

Acute Lung Injury ; chemically induced ; metabolism ; Angiopoietin-1 ; metabolism ; Angiopoietin-2 ; metabolism ; Animals ; Disease Models, Animal ; Male ; Phosgene ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effect of acute phosgene inhalation on the antioxidant enzymes, nitric oxide (NO) and nitric oxide synthase (NOS) in rats.

METHODSPhosgene was produced by decomposing bis (trichdomethyl) carbonate in the presence of N,N-dimethyl formamide. SD rats were randomly divided into two groups: control and phosgene exposure groups. In a special experimental device with equipment modulating the gas flow, phosgene exposed rats inhaled phosgene quantitatively for five minutes. Two hours later, all the rats were sacrificed and the ratio of wet weight to dried weight of lung (WW/DW) was calculated. Peripheral blood, serum and liver were collected to examine the activities of antioxidant enzymes including glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), NOS, and NO level. The total content of proteins were also determined.

RESULTSThe WW/DW ratio of lung in phosgene exposure group was much higher than that in control group (P < 0.01). The activities of GST in serum and liver of phosgene exposure group increased significantly (P < 0.05). The activities of SOD, CAT, GSHPx and NOS in serum or blood and liver of phosgene exposure group were also increased significantly (P < 0.05). But the content of NO was significantly decreased (P < 0.01).

CONCLUSIONAcute phosgene inhalation may cause a dramatically changes of several antioxidant enzyme activities, and acute injury of liver to some extent in rats. The latter is related to reactive oxygen species. But the elevation of antioxidant enzyme activities suggests that antioxidative treatment for acute phosgene poisoning should not be considered first.

Animals ; Antioxidants ; metabolism ; Chemical Warfare Agents ; poisoning ; Glutathione Peroxidase ; metabolism ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Phosgene ; poisoning ; Poisoning ; enzymology ; Random Allocation ; Rats ; Rats, Sprague-Dawley