Early stopping tends to overestimate treatment effects [12,13]; this is particularly true for studies with low event rates, as was the case in this study, in which only 12 patients in total developed ALI.What conclusions can be drawn from the paper by Determann and colleagues? sellekchem First, there are insufficient data to conclude that all ICU patients must be ventilated with a VT of 6 ml/kg. We agree with the authors who recommend that a large randomized controlled trial is needed before being able to draw this conclusion. Nonetheless, using small VTs in patients without ALI may be a reasonable strategy, and there appears to be little evidence of harm if clinicians address issues related to maintenance of sufficient positive end-expiratory pressure (PEEP), and possibly the respiratory acidosis that may arise.

Second, as hinted at above, it is interesting to speculate on the relationship between MV and ALI. If Determann and colleagues’ data are correct, should we begin to consider that ALI/ARDS is a consequence of our efforts to ventilate patients, rather than progression of the underlying disease [14]? Injurious ventilatory strategies have been shown to increase alveolar-capillary leak, worsen oxygenation, cause pulmonary infiltrates, decrease lung compliance and cause an increase in lavage and systemic cytokines – all hallmarks of ALI/ARDS. In the context of increased alveolar-capillary leak, use of excessive intravenous fluids – often used to treat shock in patients at risk for ALI – can cause increased lung water, and again worsen mechanics and gas exchange, and indeed worsen clinical outcomes.

It may not be a coincidence that ARDS was first described in the late 1960s, at the time of the Vietnam war – it is also called ‘Da Nang lung’ or ‘shock lung’ – when patients were resuscitated aggressively on the battle-field. Finally, endotracheal intubation affects host defence and can lead to development of colonization/pneumonia, a predisposing factor for ALI. As such, is ALI/ARDS largely a ‘man-made’ syndrome, and is it a consequence of the aggressive regimens we have adopted to treat acutely ill patients? If so, and if the results of Determann and colleagues vis-��-vis the marked decrease in development of ALI in patients treated with low VT turns out to be correct, it would mark an inflection point in which ALI/ARDS is no longer a syndrome that must be treated, but is a syndrome that should be prevented.

AbbreviationsALI: acute lung injury; ARDS: acute respiratory distress syndrome; MV: mechanical ventilation; VILI: ventilator-induced lung injury; VT: tidal volume.Competing interestsThe authors declare that they have no competing Drug_discovery interests.Authors’ contributionsJV and AS equally participated in the writing of the drafts and the final manuscript.NotesSee related research by Determann et al., http://ccforum.