Dexamethasone for the treatment of acute respiratory distress syndrome: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to evaluate the efficacy and safety of dexamethasone in the treatment of acute respiratory distress syndrome (ARDS). METHODS: A systematic search of electronic databases was carried out from inception to May 1, 2022, including PUBMED, EMBASE, Cochrane Library, Wangfang, VIP, and CNKI. Other searches were also checked for dissertations/theses and the reference lists of the included studies. Two team members examined all citations and selected eligible articles. Randomized controlled trials (RCTs) reporting the efficacy and safety of dexamethasone for the treatment of ARDS were included, and the quality of eligible RCTs was assessed using the Cochrane Risk of Bias Tool. If necessary, we conducted data synthesis and meta-analysis. The primary outcome was all-cause mortality. Secondary outcomes were mechanical ventilation duration (day), ventilator-free status at 28 days; intensive care unit (ICU) free (day), ICU mortality, hospital mortality, sequential organ failure assessment (SOFA) as mean and range, SOFA as No. of patients, peak airway pressure (cmH2O), arterial oxygen pressure (mm Hg), days with PaO2 > 10kPa, PaO2, and the occurrence rate of adverse events. RESULTS: Four studies involving 702 patients were included in this analysis. This study showed that dexamethasone could significantly reduce all-cause mortality (odds ratio (OR) = 0.62, 95% confidence interval (CI) [0.44, 0.88], I2 = 30%, P < .001), and decrease ventilator-free status at 28 days (MD = 3.65, 95% CI [1.49, 5.80], I2 = 51%, P < .001). No significant differences in occurrence rates of adverse events were found between dexamethasone and routine or standard care. CONCLUSIONS: Evidence from the meta-analysis suggests that dexamethasone is an effective and relatively safe treatment for all-cause mortality and ventilator-free status at 28 days in patients with ARDS. Owning to the small number of eligible RCTs, the conclusions of present study are warranted in the future study.

Insulin upregulates the expression of epithelial sodium channel in vitro and in a mouse model of acute lung injury: role of mTORC2/SGK1 pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by proteinaceous pulmonary edema and severe arterial hypoxemia with a mortality of approximately 40%. Stimulation of epithelial sodium channel (ENaC) promotes Na(+) transport, a rate-limiting step for pulmonary edema reabsorption. Insulin is known to participate in the ion transport; however, its role in pulmonary edema clearance and the regulatory mechanism involved have not been fully elucidated. In the current study, in a lipopolysaccharide-based mouse model of ALI, we found that insulin alleviated pulmonary edema by promoting ENaC-mediated alveolar fluid clearance through serum and glucocorticoid induced kinase-1 (SGK1). In alveolar epithelial cells, insulin increased the expression of α-, ß-, and γ-ENaC, which was blocked by the mammalian target of rapamycin complex 2 (mTORC2) inhibitor or knockdown of Rictor (a necessary component of mTORC2), and SGK1 inhibitor, respectively. In addition, an immunoprecipitation study demonstrated that SGK1(Ser422) phosphorylation, the key step for complete SGK1 activation by insulin, was conducted through PI3K/mTORC2 pathway. Finally, we testified the role of mTORC2 in vivo by demonstrating that PP242 prevented insulin-stimulated SGK1 activation and ENaC increase during ALI. The data revealed that during ALI, insulin stimulates alveolar fluid clearance by upregulating the expression of α-, ß-, and γ-ENaC at the cell surface, which was, at least, partially through activating mTROC2/SGK1 signaling pathway.