A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome:: A randomized, controlled trial

Objective. It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (P-flex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS). Design: Randomized, controlled clinical trial. Setting: Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: Espana Study). Patients: All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the PaO2/FiO(2) remained <= 200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pf(lex/)LTV. Interventions., In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP >= 5 cm H2O. In the P-flex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at P-flex + 2 cm H2O. In both groups, FIO2 was set to maintain arterial oxygen saturation >90% and PaO2 70-100 mm Hg, and respiratory rate was adjusted to maintain PaCO2 between 35 and 50 mm Hg. Measurements and Main Results. The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 P-flex), eight patients (five in control, three in P-flex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p =.040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p =.041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in P-flex/LTV, p =.008) all favored P-flex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p <.001). Conclusions: A mechanical ventilation strategy with a PEEP level set on day 1 above P-flex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS.