The magnitude of the clinical burden of VILI was shown by the recent ARDSnet trial in which 861 patients with ARDS were randomised to receive either a "traditional" tidal volume (12 ml/kg predicted body weight) or a low tidal volume strategy (6 ml/kg).2 Mortality was 39.8% in the traditional group and 31% in the low volume group. In other words, at least 8.8% of the absolute mortality from ARDS is attributable to VILI. A considerable amount of attention is currently directed at the potential clinical benefits of improving and maintaining lung recruitment, based on the theories outlined above, using higher levels of PEEP or HFOV

It is interesting to speculate on precisely how VILI increases mortality. The injury to the lung described in experimental models probably occurs in humans, to a greater or lesser degree. However, most deaths in ARDS are from MSOF rather than respiratory failure.101 It is therefore likely that mechanical ventilation can influence the development of MSOF, possibly through the release of proinflammatory mediators, as described above. Two recent clinical studies add weight to this hypothesis. Ranieri and coworkers examined the effect of two ventilatory strategies on cytokine levels in ARDS. Forty four patients were randomised either to a "protective" strategy, in which the PEEP and tidal volume were set such that tidal ventilation occurred exclusively between the lower and upper inflection points of the pressure volume curve (see fig 8.1), or a "control" strategy in which the tidal volume was set to obtain normal values of arterial CO2 and the PEEP set to produce the greatest improvement in arterial oxygen saturation without worsening haemodynamics. The protective group had significantly lower levels of plasma and bronchoalveolar lavage cytokines and significantly less organ failure.92 102 Along similar lines, the ARDSnet study found that plasma levels of IL-6 fell significantly more in patients ventilated with the lower than the traditional tidal volume.2 It therefore seems likely that mechanical ventilation in ARDS can promote systemic inflammation and multiorgan failure. Crucially, however, it is not known which factor(s) are responsible for mediating this detrimental effect and how they exert a toxic effect on distal organs.

In addition to increasing mortality in ARDS, VILI may contribute to the persistent lung function abnormalities (principally a restrictive defect with abnormal transfer factor) seen in a minority of survivors.103 However, no studies to date have shown that protective ventilatory strategies in ARDS are associated with improved long term lung function.104

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