Feasibility and safety of ultra-low tidal volume ventilation without extracorporeal circulation in moderately severe and severe ARDS patients.

PURPOSE: Mechanical ventilation with ultra-low tidal volume (VT) during ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury, with the main drawback of worsening respiratory acidosis. We hypothesized that VT could be reduced down to 4 ml/kg, with clinically significant decrease in driving pressure, without the need for extracorporeal CO2 removal, while maintaining pH > 7.20. METHODS: We conducted a non-experimental before-and-after multicenter study on 35 ARDS patients with PaO2/FiO2 ≤ 150 mmHg, within 24 h of ARDS diagnosis. After inclusion, VT was reduced to 4 ml/kg and further adjusted to maintain pH ≥ 7.20, respiratory rate was increased up to 40 min-1 and PEEP was set using a PEEP-FiO2 table. The primary judgment criterion was driving pressure on day 2 of the study, as compared to inclusion. RESULTS: From inclusion to day 2, driving pressure decreased significantly from 12 [9-15]  to 8 [6-11] cmH2O, while VT decreased from 6.0 [5.9-6.1] to 4.1 [4.0-4.7] ml/kg. On day 2, VT was below 4.2 ml/kg in 65% [CI95% 48%-79%], and below 5.25 ml/kg in 88% [CI95% 74%-95%] of the patients. 2 patients (6%) developed acute cor pulmonale after inclusion. Eleven patients (32%) developed transient severe acidosis with pH < 7.15. Fourteen patients (41%) died before day 90. CONCLUSION: Ultra-low tidal volume ventilation may be applied in approximately 2/3 of moderately severe-to-severe ARDS patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients.

Protective effect of thioredoxin upon NO-mediated cell injury in THP1 monocytic human cells.

Although NO has been postulated to play important roles in host defences, it is potentially damaging for exposed cells, including for the macrophages producing the NO. Thus a network of radical acceptors and enzymes is thought to play an important redox-buffering role to protect cells against NO-mediated injury. We examined the properties of the redox systems superoxide dismutase (SOD)/catalase, glutathione (GSH) and thioredoxin (Trx), in regulating the viability of two human monocytic cell lines (THP1 and U937) exposed to the NO-generating compound diethylene triamine-nitric oxide (DETA-NO). We observed that NO-induced cytotoxic effects were time- and dose-dependent towards the two cell lines. After vitamin-induced differentiation in vitro with retinoic acid (RA) and 1,25-dihydroxy vitamin D(3) (VD), termed RA/VD, we observed that THP1 RA/VD cells became more resistant to NO-mediated cytotoxicity whereas the susceptibility of U937 cells was not modified. Using Western blotting and reverse-transcriptase PCR methods, we observed that gene transcription and protein expression of Trx and thioredoxin reductase were significantly increased upon RA/VD treatment and differentiation in THP1 cells. By contrast, SOD/catalase and GSH redox state remained unmodified. Finally, a stable transfectant THP1 line overexpressing Trx was found to be more resistant than THP1 control cells that were untransfected or transfected with an empty plasmid, when exposed to DETA-NO in vitro. In conclusion, we observed an inverse correlation between cell susceptibility to NO damaging effects and Trx expression, suggesting that the Trx system may have important preventative capacities towards NO-mediated cellular injury in monocytic macrophage cells.