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Background Lung-protective ventilation and prolonged prone positioning (PP) are presented as essential in treating acute respiratory distress syndrome (ARDS). The optimal respirator mode, however, remains controversial. Pressure-supported spontaneous breathing (PS) during ARDS provides several advantages, but is difficult to achieve during PP because of respiratory depression as a side effect of sedative drugs. This study was designed to evaluate the feasibility and safety of PS during PP in ARDS patients sedated with inhaled sevoflurane. Results Overall, we have observed 4339 h of prone positioning in 62 patients who had a median of four prone episodes during treatment. Within 3948 h (91%), patients were successfully brought into a pressure-supported spontaneous breathing mode. The median duration of each prone episode was 17 h (IQR 3). Median duration of pressure-supported spontaneous breathing per episode was 16 h (IQR 5). Just one self-extubation occurred during 276 episodes of PP. Conclusions and implications Pressure-supported spontaneous breathing during prolonged prone positioning in intubated ARDS patients with or without ECMO can be achieved during volatile sedation with sevoflurane. This finding may provide a basis upon which to question the latest dogma in ARDS treatment. Our concept must be further investigated and compared to controlled ventilation with regard to driving pressure, lung-protective parameters, muscle weakness and mortality before it can be routinely applied.

STROBE- Checklist (shows the filled in STROBE checklist). (DOCX 20 kb)

Details of the evaluated clinical scoring systems (shows the parameters of each of the evaluated scoring systems). (DOCX 17 kb)

Additional statistical analysis (shows univariate and multivariate Analysis of potential risk factors for tracheostomy). (DOCX 20 kb)

Purpose Recently, the noble gas argon attracted significant attention due to its neuroprotective properties. However, the underlying molecular mechanism is still poorly understood. There is growing evidence that the extracellular regulated kinase 1/2 (ERK1/2) is involved in Argon´s protective effect. We hypothesized that argon mediates its protective effects via the upstream located toll-like receptors (TLRs) 2 and 4. Methods Apoptosis in a human neuroblastoma cell line (SH-SY5Y) was induced using rotenone. Argon treatment was performed after induction of apoptosis with different concentrations (25, 50 and 75 Vol% in oxygen 21 Vol%, carbon dioxide and nitrogen) for 2 or 4 hours respectively. Apoptosis was analyzed using flow cytometry (annexin-V (AV)/propidiumiodide (PI)) staining, caspase-3 activity and caspase cleavage. TLR density on the cells’ surface was analyzed using FACS and immunohistochemistry. Inhibition of TLR signaling and extracellular regulated kinase 1/2 (ERK1/2) were assessed by western blot, activity assays and FACS analysis. Results Argon 75 Vol% treatment abolished rotenone-induced apoptosis. This effect was attenuated dose- and time-dependently. Argon treatment was accompanied with a significant reduction of TLR2 and TLR4 receptor density and protein expression. Moreover, argon mediated increase in ERK1/2 phosphorylation was attenuated after inhibition of TLR signaling. ERK1/2 and TLR signaling inhibitors abolished the anti-apoptotic and cytoprotective effects of argon. Immunohistochemistry results strengthened these findings. Conclusion These findings suggest that argon-mediated anti-apoptotic and neuroprotective effects are mediated via inhibition of TLR2 and TLR4.

PLoS one 9(12), e115984 (2014). doi:10.1371/journal.pone.0115984, Published by PLoS, Lawrence, Kan.

Purpose Carbon monoxide (CO) is an accepted cytoprotective molecule. The extent and mechanisms of protection in neuronal systems have not been well studied. We hypothesized that delivery of CO via a novel releasing molecule (CORM) would impart neuroprotection in vivo against ischemia-reperfusion injury (IRI)-induced apoptosis of retinal ganglion cells (RGC) and in vitro of neuronal SH-SY5Y-cells via activation of soluble guanylate-cyclase (sGC). Methods To mimic ischemic respiratory arrest, SH-SY5Y-cells were incubated with rotenone (100 nmol/L, 4 h) ± CORM ALF186 (10–100 µmol/L) or inactivated ALF186 lacking the potential of releasing CO. Apoptosis and reactive oxygen species (ROS) production were analyzed using flow-cytometry (Annexin V, mitochondrial membrane potential, CM-H2DCFDA) and Western blot (Caspase-3). The impact of ALF186± respiratory arrest on cell signaling was assessed by measuring expression of nitric oxide synthase (NOS) and soluble guanylate-cyclase (sGC) and by analyzing cellular cGMP levels. The effect of ALF186 (10 mg/kg iv) on retinal IRI in Sprague-Dawley rats was assessed by measuring densities of fluorogold-labeled RGC after IRI and by analysis of apoptosis-related genes in retinal tissue. Results ALF186 but not inactivated ALF186 inhibited rotenone-induced apoptosis (Annexin V positive cells: 25±2% rotenone vs. 14±1% ALF186+rotenone, p