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

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response. Regrettably, the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition. Xuebijing (XBJ), a traditional Chinese medicine recognized for its potent anti-inflammatory properties, exhibits promise as a potential therapeutic agent for ALI/ARDS. This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism. To this end, we established an LPS-induced ALI model and treated ALI mice with XBJ. Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%. Moreover, XBJ substantially suppressed the production of TNF-α, IL-6, and IL-1β in the lung tissue. Subsequently, we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses. Furthermore, we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-α production. Therefore, this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-α release.
Animals ; Mice ; Alveolar Epithelial Cells ; Pyroptosis ; Gasdermins ; Lipopolysaccharides/adverse effects* ; Tumor Necrosis Factor-alpha ; Acute Lung Injury/drug therapy* ; Respiratory Distress Syndrome

PURPOSE: Despite improved quality of intensive care, acute respiratory distress syndrome (ARDS) significantly contributes to mortality in critically ill children. As pre-existing definitions of ARDS were adult-oriented standards, the Pediatric Acute Lung Injury Consensus Conference (PALICC) group released a new definition of pediatric ARDS. In this study, we aimed to assess the performance of PALICC definition for ARDS risk stratification. METHODS: Total 332 patients who admitted to the intensive care unit at Severance Hospital from January 2009 to December 2016 and diagnosed as having ARDS by either the PALICC definition or the Berlin definition were retrospectively analyzed. Patient characteristics and mortality rates were compared between the individual severity groups according to both definitions. RESULTS: The overall mortality rate was 36.1%. The mortality rate increased across the severity classes according to both definitions (26% in mild, 37% in moderate and 68% in severe by the PALICC definition [P<0.001]; 20% in mild, 32% in moderate and 64% in severe by the Berlin definition [P<0.001]). The mortality risk increased only for severe ARDS in both definitions (hazard ratio [95% confidence interval]: 2.279 [1.414–3.672], P=0.001 by the PALICC definition; 2.674 [1.518–4.712], P=0.001 by the Berlin definition). There was no significant difference in mortality discrimination between the 2 definitions (difference in integrated area under the curve: 0.017 [−0.018 to 0.049]). CONCLUSION: The PALICC definition demonstrated similar discrimination power on PARDS' severity and mortality as the Berlin definition.
Acute Lung Injury* ; Berlin ; Child ; Consensus* ; Critical Care ; Critical Illness ; Discrimination (Psychology) ; Humans ; Intensive Care Units ; Mortality ; Respiratory Distress Syndrome, Adult* ; Retrospective Studies

ObjectiveExposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation, leading to dyspnea, hypoxemia, airway obstruction, pneumonitis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Although bromine is less reactive and oxidative than chlorine, inhalation also results in bronchospasm, airway hyperresponsiveness, ARDS, and even death. Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well. There is no specific antidote for these injuries since the mechanisms are largely unknown.

Data SourcesThis review was based on articles published in PubMed databases up to January, 2018, with the following keywords: "chlorine," "bromine," "lung injury," and "ARDS."

Study SelectionThe original articles and reviews including the topics were the primary references.

ResultsBased on animal studies, it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity; thus, potential treatments will target the oxidative stress and inflammation induced by chlorine. Antioxidants, cAMP-elevating agents, anti-inflammatory agents, nitric oxide-modulating agents, and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury. Elevated free heme level is involved in acute lung injury caused by bromine inhalation. Hemopexin, a heme-scavenging protein, when administered postexposure, decreases lung injury and improves survival.

ConclusionsAt present, there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs.

Acute Lung Injury ; chemically induced ; Animals ; Chlorine ; toxicity ; Halogens ; toxicity ; Humans ; Lung ; drug effects ; pathology ; Respiratory Distress Syndrome, Adult ; drug therapy

BACKGROUND/AIMS: Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance. METHODS: We retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined. RESULTS: The histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate. CONCLUSIONS: The histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.
Acute Lung Injury ; Berlin ; Biopsy* ; Humans ; Korea ; Lung Diseases, Interstitial ; Lung* ; Mortality ; Pathology ; Population Characteristics* ; Respiratory Distress Syndrome, Adult* ; Retrospective Studies

ObjectiveAcute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance (AFC) in ARDS.

Data SourcesArticles published up to September 2017 were selected from the PubMed, with the keywords of "alveolar fluid clearance" or "lung edema" or "acute lung injury" or "acute respiratory distress syndrome", and "specialized pro-resolving mediators" or "lipoxin" or "resolvin" or "protectin" or "maresin" or "alveolar epithelial cells" or "aspirin-triggered lipid mediators" or "carbon monoxide and heme oxygenase" or "annexin A1".

Study SelectionWe included all relevant articles published up to September 2017, with no limitation of study design.

ResultsSpecialized pro-resolving mediators (SPMs), as the proinflammatory mediators, not only upregulated epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporins levels, but also improved Na,K-ATPase activity to promote AFC in ARDS. In addition to the direct effects on ion channels and pumps of the alveolar epithelium, the SPMs also inhibited the inflammatory cytokine expression and improved the alveolar epithelial cell repair to enhance the AFC in ARDS.

ConclusionsThe present review discusses a novel mechanism for pulmonary edema fluid reabsorption. SPMs might provide new opportunities to design "reabsorption-targeted" therapies with high degrees of precision in controlling ALI/ARDS.

Acute Lung Injury ; metabolism ; Animals ; Cystic Fibrosis Transmembrane Conductance Regulator ; metabolism ; Humans ; Respiratory Distress Syndrome, Adult ; metabolism

OBJECTIVE: To explore the incidence and risk factors for the acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) after resection of esophageal carcinoma. METHODS: We retrospectively analyzed 422 consecutive patients admitted to the Department of Critical Care Medicine with esophageal carcinoma undergoing esophagectomy from January 2010 to December 2016 in Peking University Cancer Hospital. ALI/ARDS were diagnosed, the patients were divided into ALI/ARDS group and control group without ALI/ARDS, the differences of clinical features were contrasted between the two groups, and the multivariate Logistic regression modeling was used to identify the independent risk factors for ALI/ARDS. RESULTS: In the study, 41 ALI/ARDS cases were diagnosed, making up 9.7% (41/422) of all the enrolled patients undergoing esophagectomy. Comparisons of the ALI/ARDS group and the control group indicated significant statistical differences in the average length of their hospital stay [(18.9±9.7) d vs. (14.8±3.6) d, P=0.011], the proportion of the patients who needed mechanical ventilation support [51.2% (21/41) vs. 9.4% (36/381), P<0.001] and in-hospital mortality [31.7% (13/41) vs. 5.0% (19/381), P<0.001]. Univariate analysis showed significant differences between the patients with ALI/ARDS and without ALI/ARDS in smoking history (P=0.064), preoperative forced expiratory volume in one second/forced vital capacity (FEV1/FVC) (P=0.020), diffusing capacity of the lung for carbon monoxide (DLCO) (P=0.011), body weight index (BMI) (P=0.044), American Society of Anesthesiologists (ASA) physical status classification (P=0.049) and one lung ventilation duration (P=0.008), while multivariate Logistic regression analysis indicated that preoperative FEV1/FVC (OR=1.053, P=0.016, 95%CI 1.010-1.098), ASA physical status classification (OR=2.392, P=0.033, 95%CI 1.073-5.335) and one lung ventilation duration (OR=0.994, P=0.028, 95%CI 0.989-0.999) were the independent risk factors for ALI/ARDS after esophagectomy. CONCLUSION ALI/ARDS was a serious complication in patients undergoing esophagectomy associated with increment in length of hospital stay and in-hospital mortality. Multivariate Logistic regression analysis indicated that preoperative FEV1/FVC, ASA classification and one lung ventilation duration were the independent risk factors for ALI/ARDS after esophagectomy. Carefully assessing the patient before operation, shortening one lung ventilation duration were the key points in preventing ALI/ARDS after esophagectomy.
Acute Lung Injury/etiology* ; Esophagectomy/adverse effects* ; Humans ; Respiration, Artificial ; Respiratory Distress Syndrome/etiology* ; Retrospective Studies ; Risk Factors

Critical care medicine is to provide advanced medical care to critically ill-patients threatened by severe diseases. Although critical care is a core area of surgery, surgeons have fewer interests and opportunities for participating in it, and the dedicated intensivists with other specialties have had a deeper involvement. It is difficult to recruit surgical intensivists or trauma surgeons for critical care due to the high labor intensity, high risk of medical accidents and conflicts, and inappropriate remuneration. The most common cause, however, is the lack of opportunities for surgical cases. There is a negative perception among surgeons that surgical intensivists are ‘the surgeons who do not operate.’ That makes the surgeons feel the gap between what they majored and what they practice. Acute care surgery, that is a relatively new, but more specialized surgical area including emergency surgery, trauma and critical care, can be a good alternative. Critically ill-patients who suffered from hemorrhagic shock, septic shock, acute renal injury, and acute respiratory distress syndrome need the intensive and aggressive treatments. Surgeons have been used to these invasive and aggressive procedures. Surgeons who have trained the critical care may be able to acquire the expertise, easily. The intensivists as a surgeon, who fully understands the operations, postoperative courses or complications, or the optimal time of surgery, can provide more efficient and accurate treatments for surgically critically ill-patients than any intensivists with other specialties. It is needed to change the surgeons' negative perceptions themselves with the support of the Korean Society of Surgery.
Acute Kidney Injury ; Critical Care* ; Critical Illness ; Education ; Emergencies ; Intensive Care Units ; Remuneration ; Respiratory Distress Syndrome, Adult ; Shock, Hemorrhagic ; Shock, Septic ; Surgeons

Data reported recently suggest that acute kidney injury (AKI) is a systemic disease that adversely affects the function of other organs-including the heart, lung, liver, brain and immune system-which is related to the high mortality rate of affected patients. Kidney and lung function are closely related in both health and disease. Data support deleterious bidirectional crosstalk between the lung and kidney. AKI is a common complication in patients with acute respiratory distress syndrome, and has been reported to exert adverse effects on the lungs. Mortality rates for AKI combined with acute lung injury (ALI) can be up to 80% in critically ill patients. Although AKI-associated ALI presents clinically as increased pulmonary edema, the mechanism of AKI-associated ALI extends beyond simple volume overload. Data from animal studies suggest that AKI-induced pulmonary edema is related to both cardiogenic edema (due to elevated hydrostatic pressure) and non-cardiogenic edema (due to pulmonary endothelial and epithelial cell injury caused by inflammation, oxidative stress, and apoptosis). ALI with mechanical ventilation causes a decline in renal hemodynamic function and apoptosis. Elucidation of the mechanisms of kidney-lung crosstalk would facilitate development of effective therapies and reduce the mortality rate of AKI combined with respiratory failure.
Acute Kidney Injury ; Acute Lung Injury ; Animals ; Apoptosis ; Brain ; Critical Illness ; Edema ; Epithelial Cells ; Heart ; Hemodynamics ; Humans ; Inflammation ; Kidney* ; Liver ; Lung* ; Mortality ; Oxidative Stress ; Pulmonary Edema ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; Respiratory Insufficiency

OBJECTIVETo compare the therapeutic effects of high-frequency oscillatory ventilation+pulmonary surfactant (HFOV+PS), conventional mechanical ventilation+pulmonary surfactant (CMV+PS), and conventional mechanical ventilation (CMV) alone for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in neonates.

METHODSA total of 136 neonates with ALI/ARDS were enrolled, among whom 73 had ALI and 63 had ARDS. They were divided into HFOV+PS group (n=45), CMV+PS group (n=53), and CMV group (n=38). The neonates in the first two groups were given PS at a dose of 70-100 mg/kg. The partial pressure of oxygen (PaO), partial pressure of carbon dioxide (PaCO), PaO/fraction of inspired oxygen (FiO), oxygenation index (OI), and respiratory index (RI) were measured at 0, 12, 24, 48, and 72 hours of mechanical ventilation.

RESULTSAt 12, 24, and 48 hours of mechanical ventilation, the HFOV+PS group had higher PaOand lower PaCOthan the CMV+PS and CMV groups (P<0.05). At 12, 24, 48, and 72 hours of mechanical ventilation, the HFOV+PS group had higher PaO/FiOand lower OI and RI than the CMV+PS and CMV groups (P<0.05). The HFOV+PS group had shorter durations of mechanical ventilation and oxygen use than the CMV+PS and CMV groups (P<0.05). There were no significant differences in the incidence rates of air leakage and intracranial hemorrhage and cure rate between the three groups.

CONCLUSIONSIn neonates with ALI/ARDS, HFOV combined with PS can improve pulmonary function more effectively and shorten the durations of mechanical ventilation and oxygen use compared with CMV+PS and CMV alone. It does not increase the incidence of complications.

Acute Lung Injury ; physiopathology ; therapy ; Combined Modality Therapy ; Female ; High-Frequency Ventilation ; Humans ; Infant, Newborn ; Male ; Pulmonary Surfactants ; therapeutic use ; Respiratory Distress Syndrome, Newborn ; physiopathology ; therapy ; Respiratory Mechanics