Titrating PEEP using esophageal pressures did not improve ARDS outcomes (EPVent-2)
In acute respiratory distress syndrome (ARDS), using pleural pressure to adjust positive end-expiratory pressure (PEEP) has long been considered a cumbersome but theoretically ideal technique to optimize ventilator management. Using esophageal pressure as a surrogate for pleural pressure can allow one to calculate and minimize the transpulmonary pressure gradient, elevations in which are the putative cause of ventilator-induced lung injury. But in a new randomized trial dubbed EPVent-2, titrating PEEP according to the esophageal pressure provided no clear benefits over empirical adjustment tending toward relatively high PEEP. The results were published in JAMA. Two hundred patients at 14 centers with moderate-to-severe ARDS were randomly assigned to either esophageal pressure-guided PEEP titration, or empirical high-PEEP strategy. (How high? They used tables from trials testing high-frequency oscillatory ventilation, e.g., 18 cm H2O of PEEP at FiO2 0.4 - 0.5, and 20 of PEEP for FiO2 0.5 - 0.8.) All patients could get neuromuscular blockade, sedation, and volume resuscitation according to their treating physicians. Prone positioning was only used as salvage therapy (the Proseva trial had not yet been published when this trial was designed). In practice, patients in both groups received very similar doses of PEEP for any given FiO2. There was no difference in groups in the primary outcome, a ranked composite score including death and ventilator-free days, nor in secondary outcomes such as 28-day mortality, ICU length of stay, etc. However, significantly fewer patients receiving esophageal pressure-guided PEEP required rescue therapy (4 vs 12). Barotrauma occurred in equivalent numbers of patients (5 vs 6). The results stand in contrast to a prior study (EPVent) which did show improved oxygenation and a trend toward improved survival with an esophageal pressure-guided PEEP strategy.
What This Means
Any remaining margins for improvement in ventilator management of ARDS seem to be very slim indeed. Esophageal-pressure titration of PEEP was widely considered ideal, but provided no clear advantage for most patients. That said, it's possible that ~8 patients (8%) were saved from requiring rescue therapy, which is something (confidence intervals were 0.8 to 15% on this absolute difference, so it was probably at least one person). Uncertainty persists on the ideal PEEP strategy for patients in ARDS (which is why this study was conceived and performed). That's because there is no single ideal strategy. High PEEP is currently suggested for patients with more-severe ARDS, but high PEEP might sometimes be harmful in less-severe ARDS. In one sense the EPVEnt-2 trial provides a fresh slate for researchers. Since most patients with severe ARDS should be prone, future trials will need to examine the ideal PEEP strategy in prone position. More than ventilator-tweaking, prone positioning is now the most hopeful frontier in improving outcomes from ARDS. Given the benefits observed with prone positioning, and its inclusion in society guidelines, one would have expected it to have swept the world faster than the Spanish flu. In a future post we'll explore the reasons why that hasn't happened. Source: JAMA