The main difference between our study and earlier studies [6-10] is that the patients received lung-protective mechanical ventilation according to a strict protocol.Mortality and ventilator-associated pneumoniaThe excess mortality potentially associated with VAP in patients with severe ARDS is difficult to assess, because many factors may contribute to death in such patients. The selleckchem Enzastaurin management of ARDS has changed over the last 15-year period. Lung-protective mechanical ventilation is now the standard of care. This change may contribute to explaining the differences in ICU mortality between our study (41.8% versus 30.7% with and without VAP, respectively) and previously published studies [6-8] (52% to 78% versus 59% to 92% with and without VAP, respectively), which occurred despite similar baseline severity scores (Table (Table7).

7). However, improvements have occurred in general ICU care and mortality in many other critical illnesses during recent years.Risk factors for VAPOnly male sex and the admission Glasgow Coma Scale score were independently associated with an increased risk of developing a bacterial VAP in our patients with severe ARDS. In a study of 5,081 patients, Combes et al. [19] found that nosocomial pneumonia was more common in men than in women (51% versus 44%; P = 0.01). In a large US database including 9,080 patients, male gender was an independent risk factor for VAP. Differences in VAP risk between men and women may be related to differences in sex hormones [20], to sex-related polymorphisms affecting immune responses to bacterial agents [21], to differences in the distribution of pathogens responsible for infections, to differences in chronic comorbidities [22], and/or to differences in the level of care [23].

Severity of illness, and most notably neurologic failure [24-29], is associated with an increased risk of VAP. Finally, routine NMBA use during the early phase of ARDS was not associated with the risk of VAP. This is in contrast with some previous studies [25,30,31], in which NMBA use (for whatever duration) in nonselected mechanically ventilated ICU patients was associated with a higher risk of VAP.Study limitationsAs stated in the ACURASYS study report [12], only 339 of 1,326 patients with severe ARDS assessed for eligibility were included. However, the vast majority of the remaining 987 patients had exclusion criteria.

The strictly standardized ventilation protocol and strategy for VAP diagnosis are major strengths of our study. Viral pneumonia was not evaluated, as some of the participating centers did not routinely perform viral studies. A study of the impact of viral infection on outcomes of ARDS patients might be of interest.ConclusionsIn those Batimastat with severe ARDS, patients ventilated according to a standardized lung-protective strategy, the development of VAP was associated with a higher risk for dying in the ICU. However, no relation to ICU death was found after adjustment.