SAN DIEGO — Mechanical ventilation with esophageal pressure-guided positive end-expiratory pressure (PEEP) did not improve the primary outcome in the EPVent-2 trial versus the use of PEEP guided by a high PEEP-fraction of inspired oxygen (FIO2) table in patients with moderate-to-severe acute respiratory distress syndrome (ARDS).
The trial’s primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28, explained Jeremy Beitler, MD, MPH, of the University of California, San Diego, in a presentation at the Society of Critical Care Medicine’s annual meeting.
The primary composite endpoint was not significantly different between treatment groups with a probability of more favorable outcome with esophageal pressure-guided PEEP of 49.6% (95% CI 41.7%-57.5%, P=0.92), as reported at the meeting and simultaneously in JAMA.
No significant difference in patient deaths within 28 days between those undergoing esophageal pressure-guided PEEP versus PEEP-FIO2 (32.4% vs 30.6%, respectively, P=0.88), and no difference was observed in terms of the number of days survivors were free from mechanical ventilation (22 vs 21 days).
However, the esophageal pressure-guided PEEP group was significantly less likely to require rescue therapy (risk difference −8.3%, 95% CI −15.8% to −0.8%, P=0.04), researchers reported.
While the authors wrote that the findings “do not support” esophageal pressured-guided PEEP titration in ARDS, “The search for a strategy to individualize ventilation settings based on patient-specific risk is ongoing, and while this trial did not provide a definitive answer on how to do that, I think that is the right question for the field to be asking,” Beitler told MedPage Today. “How do we provide the right balance between risk and benefit of certain ventilation strategies in these patients with ARDS?”
The standard of care for patients with moderate to severe ARDS involves the National Heart, Lung, and Blood Institute’s ARDS Network PEEP-FIO2 table, and Beitler noted that both treatment arms in this trial differ from usual care protocols. The study follows the 2008 EPVent trial, in which a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improved oxygenation and compliance versus standard of care.
Life-saving mechanical ventilation can be injurious and cause fatal lung injuries, which may indicate that a strategy such as esophageal pressure-guided PEEP could be beneficial, stated Alexandre Biasi Cavalcanti, MD, PhD, of the HCor Research Institute in Sao Paolo, and colleagues, in an accompanying editorial.
Although the present study does not confirm this strategy was superior, Cavalcanti’s group wrote that an important message for clinicians is that for most patients with moderate to severe ARDS, “the use of a simple and widely available tool to adjust PEEP will result in similar clinical outcomes to those of a more invasive, costly, and cumbersome strategy.”
Specifically, they noted that the authors required a 10% absolute reduction in mortality as well as 2 ventilator-free days to reach statistical significance. However, assuming the mortalities attributable to ventilator-induced lung injury is 10% would indicate that all deaths due to ventilator-induced lung injury “would need to be avoided by using the esophageal pressure-guided PEEP titration compared with the empirical high PEEP-FIO2 table,” they noted.
“The consequences of assuming such a large treatment effect were the calculation of a small required sample size and the generation of wide confidence intervals around important clinical outcomes,” they wrote. “For example, the 95% CI for the effect on 28-day mortality is compatible with both an 11.1% reduction and a 14.6% increase in mortality with the esophageal pressure-guided PEEP strategy.”
EPVent-2 enrolled patients (≥16 years) with moderate to severe ARDS (PaO2:FIO2 ≤200 mm Hg) across four hospitals in the U.S. and Canada. Patients with contraindication to esophageal instrumentation or high PEEP were excluded. Researchers used an algorithm to randomize eligible patients 1:1 to either PEEP titration strategy.
In total, 102 patients underwent esophageal pressure-guided PEEP titration and 98 were assigned to the PEEP-FIO2 group. Patients in the two groups were similar in age (58 and 57.5, respectively), and had similar Acute Physiology and Chronic Health Evaluation scores (27 vs 28) and Sequential Organ Failure Assessment scores (both 11). The PEEP-FIO2 group had more female patients (54% vs 38%).
The authors reported that other secondary outcomes, such as functional status at 1 year and all-cause mortality at 28 days, 60 days, and 1 year, did not differ between the two groups.
For adverse events, shock-free days through day 28 did not significantly differ between the two groups (median 14 vs 17 for FIO2 arm), nor did the incidence of pneumothorax (2.9% vs 2.0%, respectively) and barotrauma (5.9% vs 5.1%).
Acute kidney injury requiring initiation of renal replacement therapy in the first 28 days was numerically lower in the group of patients assigned to esophageal pressure-guided PEEP (21% vs 33.3%, P=0.056).
Study limitations included the fact that it was unclear whether the comparator arm was comparable to usual care, the authors noted. Additionally, the trial was not powered to detect clinically important treatment effects, and differences in patient biology may have an effect on ARDS patients’ therapeutic response. The study may also have been limited by methodological issues involving transpulmonary and esophageal pressure measurements that could have obstructed the intervention.
The study was supported by the National Heart, Lung, and Blood Institute (NHLBI).
Beitler and co-authors disclosed support from NHLBI. Some co-authors disclosed support from the Department of Defense, the Agency for Healthcare and Research Quality, CardioMed Consultants, and Hamilton Medical.
Cavalcanti disclosed no relevant relationships with industry. A co-author disclosed a relevant relationship with Drager.