A = missing data analysed as random, P = 0.005. B = last observation …The PEEP was higher in the PHARLAP group over the first 24 hours (Table (Table2)2) and throughout the 7 days (PHARLAP 12 �� 0.5 cm H2O, control 9.5 �� 0.5, P = 0.004, NSC 125973 Table Table3)3) than the control group.Table 2Respiratory variables during the first 24 hrs of treatment (mean �� SE)Table 3Respiratory variables during seven days of treatment (mean �� SE) * P < 0There were no other significant differences between the groups (Table (Table3)3) in respiratory and haemodynamic variables, peak or plateau pressures, pH, PaCO2 or SOFA scores during the seven-day period. Of note, the mean plateau pressures were less than 30 cm H2O throughout the study in both groups and the plateau pressures were no higher in the PHARLAP group than the control group.

There were no differences in length of ventilation, length of stay in ICU and length of stay in hospital, or hospital survival (Table (Table44).Table 4OutcomesDiscussionThis pilot, randomised controlled study examined the efficacy and safety of a multi-faceted open lung mechanical ventilation strategy that included permissive hypercapnia, staircase recruitment manoeuvres, decremental PEEP titration, low airway pressure and pressure control ventilation in patients with ARDS. The strategy appeared safe and was associated with ameliorations in plasma IL-8 and TNF-�� levels, improved static lung compliance and improved oxygenation over a seven-day period.

Although some cytokines were not significantly ameliorated (IL-6 and IL-1��) and unsurprisingly given the size of the study there were no significant differences in duration of mechanical ventilation, ICU stay and hospital stay.Static lung compliance decreased by nearly 30% in the control strategy group over the first 24 hours and remained low for the duration of the study compared with the PHARLAP strategy, which actually resulted in an increase in compliance. These suggest a greater degree of lung recruitment was sustained throughout the study period in the PHARLAP group, an effect which may be important in ARDS to minimise the potential negative effects of ventilator induced lung injury.Systemic arterial oxygenation, as measured by the PaO2/FIO2, was improved by the PHARLAP strategy and maintained for seven days.

The beneficial effects of PEEP on oxygenation have been demonstrated by systematic review and include an association with improved survival in patients with ARDS [8]. It is unclear from our results whether the improved oxygenation was as a result of the increased PEEP, the SRM, both, or another aspect Brefeldin_A of our multi-pronged strategy. However, the results of this trial expand on the previous work by our group which demonstrated that the SRM with decremental optimal PEEP titration improved lung compliance and oxygenation over a one hour period in patients with ARDS [16].