BackgroundAcute respiratory distress syndrome is characterized by damage to the lung caused by various insults, including ventilation itself, and tidal hyperinflation can lead to ventilator induced lung injury (VILI). We investigated the effects of a low tidal volume (VT) strategy (VT ≈ 3 ml/kg/predicted body weight [PBW]) using pumpless extracorporeal lung assist in established ARDS.MethodsSeventy-nine patients were enrolled after a ‘stabilization period’ (24 h with optimized therapy and high PEEP). They were randomly assigned to receive a low VT ventilation (≈3 ml/kg) combined with extracorporeal CO2 elimination, or to a ARDSNet strategy (≈6 ml/kg) without the extracorporeal device. The primary outcome was the 28-days and 60-days ventilator-free days (VFD). Secondary outcome parameters were respiratory mechanics, gas exchange, analgesic/sedation use, complications and hospital mortality.ResultsVentilation with very low VT’s was easy to implement with extracorporeal CO2-removal. VFD’s within 60 days were not different between the study group (33.2 ± 20) and the control group (29.2 ± 21, p = 0.469), but in more hypoxemic patients (PaO2/FIO2 ≤150) a post hoc analysis demonstrated significant improved VFD-60 in study patients (40.9 ± 12.8) compared to control (28.2 ± 16.4, p = 0.033). The mortality rate was low (16.5 %) and did not differ between groups.ConclusionsThe use of very low VT combined with extracorporeal CO2 removal has the potential to further reduce VILI compared with a ‘normal’ lung protective management. Whether this strategy will improve survival in ARDS patients remains to be determined (Clinical trials NCT 00538928).Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-012-2787-6) contains supplementary material, which is available to authorized users.

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IntroductionTreatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions.MethodsC57Bl/6 mice were exposed to aerosolized LPS (500 µg/ml) for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice.ResultsSimvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance.ConclusionSimvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.

The same degree of hypoxemia induced in a lavage model of acute lung injury results in greater brain damage assessed by S-100 protein and histopathologic findings when compared to a group in which hypoxemia at the same degree was induced by reducing the inspired oxygen fraction. This suggests that acute lung injury leads to neuropathologic changes independent of hypoxemia.