Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure–Guided Strategy vs an Empirical High PEEP-Fio₂ Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome

Abstract

Importance: Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS). Objective: To determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empiric high PEEP-FiO2 in moderate-to-severe ARDS. Design, Setting, and Participants: Phase-II randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged ≥ 16 years with moderate-to-severe ARDS (PaO2:FiO2 ≤ 200) were enrolled between October 31, 2012 and September 14, 2017; long-term follow-up completed July 30, 2018. Interventions: Participants were randomized to PES-guided PEEP (n = 102) or empiric high PEEP-FiO2 (n = 98). All participants received low tidal volumes. Main Outcomes and Measures: The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Pre-specified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy. Results: Two hundred patients were enrolled (mean [SD] age 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite endpoint was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% [95% CI 41.7% to 57.5%]; p = 0.92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 33 of 98 patients (30.6%) assigned to empiric PEEP-FiO2 died (risk difference 1.7% [95% CI −11.1% to 14.6%]; p = 0.88). Days free from mechanical among survivors was not significantly different (22 [15-24] vs. 21 [16.5-24] days; median difference 0 [95% CI −1 to 2] days; p = 0.85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs. 12/98 [12.2%]; risk difference −8.3% [95% CI −15.8% to −0.8%]; p = 0.04). None of the seven other pre-specified secondary clinical endpoints were significantly different. Adverse events included gross barotrauma, which occurred in six patients with PES-guided PEEP and five patients with empiric PEEP-FiO2. Conclusions and Relevance: Among patients with moderate-to-severe ARDS, PES-guided PEEP, compared to empiric high PEEP-FiO2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in ARDS. Trial Registration: ClinicalTrials.gov identifier

Ventilatory support and mechanical properties of the fibrotic lung acting as a “squishy ball”

“…Physiologic studies confirmed that P L estimated by esophageal manometry reflects the regional P L of dependent lung areas where atelectasis predominate [28,29]. Titrating PEEP to target a positive P L at end-expiration maximizes lung recruitment and improves respiratory mechanics and oxygenation in ARDS [30], but did not improve survival in ARDS when compared to empirical high PEEP [31]. This particular technique is one of the methods proposed to achieve an "open lung approach".…”

Treatment for severe acute respiratory distress syndrome from COVID-19

“…Insertion of an oesophageal balloon to measure transpulmonary pressures to set an optimal positive end-expiratory pressure can be considered in patients with moderate-to-severe obesity, although a 2019 trial in patients with ARDS did not show the benefit of this procedure in most patients. 7 Fluid management is important to consider as a measure to reduce pulmonary oedema. 8 In the absence of shock, fluid conservative therapy is recommended to achieve a negative fluid balance of 0·5 to 1·0 L per day.…”

A lung rescue team improves survival in obesity with acute respiratory distress syndrome

“…The largest epidemiologic study on ARDS was conducted in 2016 and reported an overall ICU mortality of 35.3% (95%CI 33.3%-37.2%) and hospital mortality of 40.0% (95CI 38.1%-42.1%) [7], similar to what we observed in the standard protocol-based cohort treated according to the ARDSnet protocol. In 2019, two large randomized US trials in ARDS reported a mortality rate at 1 year of 44% [26] and at 90 days of 42% [25]. MGH was part of those two studies.…”

“…Further, as mentioned in the "Methods", none of our patients were enrolled in any MGH clinical trials. Although we cannot exclude other factors beyond our knowledge that might have affected the outcomes in the two cohorts, we know that, accounting for patients enrolled in trials, ARDS mortality did not change at MGH over the past 10 years (unpublished data) and did not change in the most recent US ARDS trials [25,26].…”