BackgroundThe efficacy of sivelestat in the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has not been established. In part, this is due to the wide variety of factors involved in the etiology of ALI/ARDS. In this study, we examined the efficacy of sivelestat in patients with ALI/ARDS associated with abdominal sepsis.MethodsThe subjects were 49 patients with ALI/ARDS after surgery for abdominal sepsis. The efficacy of sivelestat was retrospectively assessed in two treatment groups, ie, a sivelestat group (n = 34) and a non-sivelestat group (n = 15).ResultsThe sivelestat group showed significant improvements in oxygenation, thrombocytopenia, and multiple organ dysfunction score. The number of ventilator days (6.6 ± 6.1 versus 11.1 ± 8.4 days; P = 0.034) and length of stay in the intensive care unit (8.5 ± 6.2 versus 13.3 ± 9.5 days; P = 0.036) were significantly lower in the sivelestat group. The hospital mortality rate decreased by half in the sivelestat group, but was not significantly different between the two groups.ConclusionAdministration of sivelestat to patients with ALI/ARDS following surgery for abdominal sepsis resulted in early improvements of oxygenation and multiple organ dysfunction score, early ventilator weaning, and early discharge from the intensive care unit.

Previous studies suggest that propofol and sevoflurane anaesthesia in rats may have variable effects on the proteome. Brains from untreated rats and rats anaesthetised with intravenous propofol infusion or inhaled sevoflurane were collected at various time points post-anaesthesia and subjected to global protein expression profiling using two-dimensional gel electrophoresis. Significant changes in protein spot intensity (i.e. expression) between the propofol and sevoflurane groups demonstrated clear similarities and differences in proteomic regulation by these anaesthetics. The proteins regulated were broadly classified into groups involved in cytoskeletal/neuronal growth, cellular metabolism, signalling, and cell stress/death responses. Proteins concerned with cell death and stress responses were down-regulated by both agents, but the anaesthetics had variable effects on proteins in the other groups. Importantly, proteins such as Ulip2 and dihydropyrimidinaselike-2 were regulated in opposite directions by propofol and sevoflurane. Moreover, the timecourse of regulation of proteins varied depending on the agent used. These data suggest different underlying mechanisms of proteomic regulation. We found that sevoflurane anaesthesia had more pronounced effects, on a wider range of proteins, and over an apparently longer duration than propofol. Thus, sevoflurane could be considered a more disruptive anaesthetic agent. Our findings show that protein expression is regulated differentially according to the anaesthetic agent and the method of delivery support and extend our previous observations of differential genomic regulation by anaesthetics in the brain. This study highlights the power of proteomic studies in assessing the effects of certain anaesthetics on the integrity of neuronal structure and function.The utility of general anaesthetics is unquestioned, and their harmlessness with regard to mortality and morbidity has been evaluated and endorsed by clinical outcomes (3,(10)(11)(12)24). Little is known, however, regarding their comprehensive influence at the genomic or proteomic level, which is not reflected in mortality and morbidity. A number of genomic studies have been published, and we have shown that general anaesthesia alters gene expression, especially expression of genes involved in circadian rhythms and drug metabolism. For instance, we found persistent suppression of the expression of several genes implicated in circadian rhythms (e.g., Per2, Dbp, Egr1, Krox20 and NGF1-B) following treatment of rats with sevoflurane (20) and propofol or dexmedetomidine (41). We have also reported changes in the expression of drug metabolising enzymes in rats (e.g., Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2) in response to sevoflurane, isoflurane, propofol, or dexmedetomidine anaesthesia (30, 37) The observed changes varied depending on the identity of the anaesthetic used, and also on the mode of administration (inhaled vs. intravenous). Therefore, it is clear that anaesthetics have significant effects...